The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogs in prostate cancer | Actas Urológicas Españolas (English Edition)

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La colina es introducida en la célula a través de transportadores específicos, y una vez en su interior es fosforilada por la enzima colina-cinasa para dar lugar a la fosfocolina. Este es el primer paso de los 3 que componen la cascada enzimática conocida como vía de Kennedy, cuyo producto final es la fosfatidilcolina o lecitina. La fosfatidilcolina —principal fosfolípido de membrana— es sintetizada en 2 pasos mediante una reacción catalizada por la fosfocolina citidiltransferasa y a través de la fosfocolina transferasa." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.M. Navarro-Pelayo Láinez, A. Rodríguez-Fernández, M. Gómez-Río, F. Vázquez-Alonso, J.M. Cózar-Olmo, J.M. Llamas-Elvira" "autores" => array:6 [ 0 => array:2 [ "nombre" => "M.M." "apellidos" => "Navarro-Pelayo Láinez" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez-Fernández" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Gómez-Río" ] 3 => array:2 [ "nombre" => "F." 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Primitive neuroectodermal tumor from a mixed germ cell tumor. (A) Gross anatomy. (B) Microscopic view showing diffuse neuroepithelial overgrowth changing the testicular parenchyma (10×). C. Higher magnification (40×) reveals a proliferation of monotonous round cells with prominent rosette formation. II. A. Gross appearance of an osteosarcoma from a mixed germ cell tumor, which shows a typical heterogeneous mixed germ cell tumor. B and C. Photomicrograph showing a spindle cell proliferation with a deposit of osteoid matrix with malignant characteristics (40×). III. (A) Macroscopic sample of an intestinal-type adenocarcinoma from a mixed germ cell tumor. (B) Panoramic photomicrograph showing the haphazard proliferation of glands (5×). (C) Intestinal type glands with desmoplastic reaction (10×). IV. (A) Gross appearance of a teratoma with malignant transformation to rhabdomyosarcoma and chondrosarcoma. (B) Malignant cartilaginous component is observed, with increased cellularity and atypia; besides this there is a sarcomatoid appearance with muscle differentiation (10×). (C) Cells with muscle differentiation strongly positive for desmin (40×). (D) The higher the magnification (40×), the cartilaginous component highlights the presence of atypia and mitosis. (E) Rhabdomyosarcoma component (40×), spindle cell proliferation, atypia, and hyperchromatic nuclei, abundant eosinophilic cytoplasm with displacement of the core, which were strongly positive for desmin." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. García-Labastida, G.S. Gómez-Macías, J.P. Flores-Gutiérrez, M. Ponce-Camacho, J. Ancer-Rodríguez, O. Barboza-Quintana, R. Garza-Guajardo" "autores" => array:7 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "García-Labastida" ] 1 => array:2 [ "nombre" => "G.S." "apellidos" => "Gómez-Macías" ] 2 => array:2 [ "nombre" => "J.P." 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Chenlo, S.M. Curi, M.N. Pugliese, J.I. Ariagno, M. Sardi-Segovia, M.J. Furlan, H.E. Repetto, E. Zeitler, M. Cohen, G.R. Mendeluk" "autores" => array:10 [ 0 => array:2 [ "nombre" => "P.H." "apellidos" => "Chenlo" ] 1 => array:2 [ "nombre" => "S.M." "apellidos" => "Curi" ] 2 => array:2 [ "nombre" => "M.N." "apellidos" => "Pugliese" ] 3 => array:2 [ "nombre" => "J.I." "apellidos" => "Ariagno" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Sardi-Segovia" ] 5 => array:2 [ "nombre" => "M.J." "apellidos" => "Furlan" ] 6 => array:2 [ "nombre" => "H.E." "apellidos" => "Repetto" ] 7 => array:2 [ "nombre" => "E." "apellidos" => "Zeitler" ] 8 => array:2 [ "nombre" => "M." "apellidos" => "Cohen" ] 9 => array:2 [ "nombre" => "G.R." 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Navarro-Pelayo Láinez, A. Rodríguez-Fernández, M. Gómez-Río, F. Vázquez-Alonso, J.M. Cózar-Olmo, J.M. Llamas-Elvira" "autores" => array:6 [ 0 => array:4 [ "nombre" => "M.M." "apellidos" => "Navarro-Pelayo Láinez" "email" => array:1 [ 0 => "mnavarropelayo@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Rodríguez-Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Gómez-Río" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "F." "apellidos" => "Vázquez-Alonso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "J.M." "apellidos" => "Cózar-Olmo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "J.M." "apellidos" => "Llamas-Elvira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Urología, Hospital Universitario Virgen de las Nieves, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Papel de la tomografía por emisión de positrones/tomografía computarizada con análogos radiomarcados de colina en el cáncer de próstata" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1399 "Ancho" => 1808 "Tamanyo" => 276901 ] ] "descripcion" => array:1 [ "en" => "73-Year-old patient with newly diagnosed prostate cancer (PSA: 11.95ng/ml; Gleason: 4+5; clinical stage: T3a) under study due to initial staging. 18F-fluorocholine-PET/CT examination shows in its axial sections of PET (A), CT (B), and fusion (F) a focal increase of uptake in the left lobe of the prostate gland (maxSUV: 6.72), compatible with the neoplastic activity already known at this location." ] ] ] "textoCompleto" => "IntroductionEpidemiologyProstate cancer (PC) is one of the most important medical problems of the male population today. It is the most common solid tumor in the European Union and it causes a significant number of deaths in industrialized countries.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>The diagnostic instruments to obtain signs of this cancer include digital rectal examination (DRE), serum prostate specific antigen (PSA) concentration, and transrectal ultrasound; however, definitive diagnosis is based on the presence of adenocarcinoma in the prostate biopsy.Initial stagingLocal staging (T staging) of PC is based on the results of TR and MR. Possibly the latter is the technique of choice for the correct delimitation of its extension, as the new techniques—endorectal coils, spectroscopy, and combination of MR with dynamic contrast and enhanced MR in T2—offer better results in terms of PC staging.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>The nodal status (N staging) is especially important when a potentially curative treatment is expected. Conventional imaging tests have limitations in detection of metastases <5mm, so that the pelvic lymphadenectomy remains the most reliable method; however, it is still a controversial and invasive procedure with regard to the most appropriate technique to perform (standard or extended).<a class="elsevierStyleCrossRef" href="#bib0015">3</a>Metastatic bone site is the most frequent in PC, and the best way to evaluate it is the bone scan, which has traditionally shown a high sensitivity. In contrast, it seems not to be indicated in asymptomatic patients when the serum PSA concentration is <20ng/ml in well or moderately differentiated tumors.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>Biochemical recurrenceTumor recurrence is an event that occurs in 20–50% of patients after radical prostatectomy (RP) and in more than 30–40% of those who received external beam radiotherapy (RT). After a RP, only 2 consecutive values >0.2ng/ml represent a recurrent cancer. However, the failure of RT has been redefined several times, now being known as PSA elevation>2ng/ml above the PSA nadir. There is no consensus for the other treatments—cryotherapy or brachytherapy—and therefore it is not possible to give definite recommendations on biochemical failure in these cases.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>Only the PSA concentration and, ultimately, the RT are the only tests to routinely be performed during the follow-up. The identification and precise localization of recurrences has not yet been achieved. CT has a low sensitivity and specificity in this context, particularly if the size of the recurrence is <2cm. For its part, the MR is not a first-line diagnostic tool either, although some authors suggest that the incorporation of endorectal coils makes it a sensitive and predictive technique in identifying recurrence after RP. Bone scintigraphy is indicated in the control of symptomatic patients, but we must remember that its low specificity sometimes determines the performance of additional examinations to verify the findings.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>Radiopharmaceuticals for positron emission tomography in prostate cancerThe multimodal technique positron emission tomography/computed tomography (PET/CT), which combines the performance of the anatomical and functional scans, is emerging as a diagnostic tool useful in the study of PC.Although the most widely used radiopharmaceutical is 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG), it is not routinely used in PC. Affinity for the carbohydrate tracer is related to the glucose transporter expression of the membrane (GLUT-1), present in greater amount in the poorly differentiated hormone-independent cell lines than in well-differentiated hormone-sensitive ones. The lower uptake of 18F-FDG in PC, compared with other tumors, has been attributed to the fact that this malignancy has a slower metabolism and a lower expression of GLUT-1<a class="elsevierStyleCrossRef" href="#bib0030">6</a> transporters (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Physiological uptake of 18F-FDG is observed in viable tissues such as the brain, myocardium, liver, gastrointestinal tract, muscle, and bone marrow. Urinary excretion of the tracer is an added factor that reduces the efficiency of the technique, since the intense activity in ureters and bladder can mask injuries in the prostate and surrounding tissues.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>There is currently great interest in choline analogs. Choline is introduced into the cell via specific transporters, and once inside it is phosphorylated by the enzyme choline-kinase (CK) to yield phosphocholine. This is the first step of the 3 that make up the so-called Kennedy pathway (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) enzymatic cascade, whose final product is phosphatidylcholine or lecithin. Phosphatidylcholine, the main membrane phospholipid, is synthesized in 2 steps by means of a catalyzed reaction by phosphocholine citidiltransferase and through phosphocholine transferase. Although the specific mechanism by which the tracer uptake is produced is not sufficiently clarified, it seems to be due to 2 situations that occur in proliferative processes: increase in the transport and in the phosphorylation of choline—primarily due to the overexpression of CK—as well as increased need for lipid formation.<a class="elsevierStyleCrossRef" href="#bib0035">7</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia>No major differences were found in the biodistribution of the choline, regardless of the isotope that it is marked with (11C or 18F), except for physiological urinary elimination which is higher with 18F-fluorocholine. Under normal conditions we can find an intense tracer uptake in the liver and pancreas, being somewhat lower in the spleen, salivary and lacrimal glands. Tracer deposits in both kidneys, ureters and bladder are considered equally physiological distribution. Other less common locations but also described are the bone marrow (dorsal vertebral level) and the intestinal tract due to the high proliferation of the mucosa at this level (especially important in the small intestine).<a class="elsevierStyleCrossRef" href="#bib0040">8</a>11C-choline is indistinguishable from the natural molecule of choline; however, its short half-life (20min) causes frequent logistical problems, since it forces to work in a center near a cyclotron. Thus, it is important to have radiopharmaceuticals with greater half life as 18F-fluorocholine (110min) that can be transported to centers away from the producer cyclotron. The increased urinary excretion of 18F-fluorocholine, as explained, can alter the results of the image in the pelvis.The present review aims to critically analyze the current evidence for the use of 11C and 18F-choline-PET/CT in staging and suspected biochemical failure after treatment of PC, as well as its role as a diagnostic tool in treatment strategies during follow-up.Evidence of acquisitionTo select the bibliography used in the drafting of this article a thorough search was conducted in the scientific literature using the Medline database (via Pubmed). Relevant publications were collected by means of the inclusion of the following keywordsProstate cancer and Choline-PET, to which we added the terms Biochemical failure and/or Staging and/or PSA kinetics, arranged in different combinations. Similarly, we selected and critically reviewed the works in English and Spanish language published between 2008 and 2013. Original articles, reviews, systematic reviews, meta-analyses, and clinical practice guidelines were included. The studies published only as an abstract or the reports of the meetings were not taken into account. In general, the original ratio of bibliographic citations was discussed with all the authors to select the most relevant articles.Evidence of synthesisInitial stagingT stagingSo far choline-PET/CT is not a first-line diagnostic tool in the location of the primary tumor in patients with newly diagnosed PC.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> In this neoplasia, the presence of multiple foci of tumor is characteristic-most small-difficult to detect by PET/CT, especially those with mild uptake and size <5mm.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Moreover, its limited ability to distinguish between tumor tissue and benign prostatic diseases with affinity for the tracer (prostatitis and benign prostatic hypertrophy) often involves a high number of false positives.<a class="elsevierStyleCrossRefs" href="#bib0045">9,10</a>Because of these limitations, some groups have made technological innovations that make it possible to improve the results. The ‘double phase’ image acquisition (with late projections at 90min postinjection) enables us to differentiate between benign and malignant tissue, since over time the uptake of neoplastic lesions remains stable or even increases, decreasing in benign areas.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>An application of choline-PET/CT that increasingly becomes stronger is the location of the tumor focus in cases of high clinical suspicion of PC and at least 2 negative biopsies<a class="elsevierStyleCrossRef" href="#bib0060">12</a> in order to properly guide a new biopsy and increase the rate of detection<a class="elsevierStyleCrossRef" href="#bib0045">9</a> (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>N stagingThe choline-PET/CT is a reliable and non-invasive technique for nodal staging in patients with medium-high risk according to the D’Amico classification,<a class="elsevierStyleCrossRef" href="#bib0065">13</a> especially if we consider that conventional imaging modalities have limitations in this context.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> However, the bowel activity and physiological excretion in the urinary system (shown in the 18F-fluorocholine), along with the frequent uptake in inflammatory nodes, may interfere with the identification of the possible lymph node involvement.Most analyzed studies show high specificity but low sensitivity among their results.<a class="elsevierStyleCrossRefs" href="#bib0045">9,14</a> In a recent systematic review, values of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 66, 96, 82 and 92% respectively in the assessment of lymph nodes size >5mm.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Therefore, the choline can be useful for detecting metastatic nodal lesions of diameter ≥5mm, especially when dynamic acquisition or “dual stage”<a class="elsevierStyleCrossRef" href="#bib0075">15</a> (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>) is performed.<elsevierMultimedia ident="fig0020"></elsevierMultimedia>M stagingThe results about the usefulness of the choline-PET/CT in M staging are consistent: it is a useful technique to rule out distant metastases in patients at high risk candidates for surgical treatment.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Hodolic et al. state that the sensitivity, specificity, and diagnostic accuracy of 18F-fluorocholine in detecting bone metastases is 74.99 and 85%, respectively; moreover, they coincide with Beheshti et al. that the technique appears to be superior to bone scintigraphy by demonstrating the marrow infiltration early.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> In a recent cohort study 18F-fluorocholine modified the therapeutic approach in 20% of the patients, as it evidenced bone metastatic spread in patients with negative or inconclusive bone scintigraphy, assuming the change of therapy with curative intent to palliative.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>Again, performing delayed images is of great importance by increasing the sensitivity in the detection of bone metastases.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Biochemical recurrenceRecurrente locationAs shown in the literature, the usefulness of choline-PET/CT is clear in the detection of recurrence after RP, as well as the relationship with the value of the PSA. In fact, in the work by Breeuwsma et al. it is stated that a negative 11C-choline-PET/CT correlates with a high disease-free survival and ensures reduced need for treatment in patients with suspected recurrence after RP.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> With a threshold of standard uptake value (maxSUV)>3 and a size of tumor focus >1.7cm, the sensitivity and specificity of 11C-choline in local recurrence after RP is 73 and 88%.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Only in a recently published study that compared MRI with contrast and spectroscopy and 18F-fluorocholine-PET/CT in patients with elevation of the PSA after RP, the sensitivity of MRI is superior to that of PET in local recurrences <10mm, with similar results in >10mm.<a class="elsevierStyleCrossRef" href="#bib0100">20</a>The same cannot be said after RT, the presence of inflammatory tissue after treatment being frequent with affinity for the radiopharmaceutical. Therefore, we can not make reliable final recommendations in these patients, especially if we take into account the scarcity of published studies about it.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>The choline-PET/CT has a high PPV (86%) in the identification and location of nodal recurrence after radical treatment (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>). However, in the analysis per lesions the NPVis low, since it is not capable of detecting microscopic disease (the mean diameter of the true positives is 15mm, while that of false negatives is 6.3mm).<a class="elsevierStyleCrossRef" href="#bib0040">8</a> It is important to mention that we must be cautious in the evaluation of mediastinal lymph nodes, where the presence of inflammatory/reactive uptake is frequent.<a class="elsevierStyleCrossRef" href="#bib0105">21</a><elsevierMultimedia ident="fig0025"></elsevierMultimedia>There are studies that have compared the bone scintigraphy and PET/CT with choline during the follow-up of patients with previously treated PC. Most authors are inclined to choline analogs, showing an early assessment and a higher overall sensitivity in detecting bone metastases (30 lesions with 11C-choline were observed, not suspected by the scintigraphy, in 14.6% of the patients analyzed in the study by Fuccio et al.)<a class="elsevierStyleCrossRef" href="#bib0110">22</a> (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>). The results of another retrospective study showed a higher specificity and PPV of 11C-choline on bone scintigraphy, being so that a positive result at the bone level is reliably considered by the authors as a malignant lesion, even in the absence of confirmatory scans.<a class="elsevierStyleCrossRef" href="#bib0115">23</a><elsevierMultimedia ident="fig0030"></elsevierMultimedia>Selection of patientsNone of the risk factors for recurrence known—patient age (>65 years), time between surgery and relapse, previous biochemical failure, Gleason score, initial T and N stages—seems to influence the sensitivity of the test as the PSA value does. However, all these variables can be useful for the specialist, helping to select candidates for conducting examination.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>The authors assume that the higher the PSA value, the greater the tissue metabolism, and therefore the greater the avidity for 18F-fluorocholine,<a class="elsevierStyleCrossRef" href="#bib0125">25</a> increasing the ability to detect recurrences.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> However, in those cases where the increase of the PSA is very discreet, positive results must be validated with other techniques, taking into account that the specificity and PPV of 18F-fluorocholine-PET/CT decrease with low PSA values.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>If we analyze the works published to date, we will realize that there is no consensus about the ideal cut-off point for the PSA value. For their part, Krause et al. found a linear relationship between the value of the PSA and the positive results of the PET/CT: 36% of the studies with PSA<1ng/ml, 43% with 1≤PSA<2ng/ml, 62% with 2≤PSA<3ng/ml, and 73% with PSA≥3ng/ml.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> Other works, like the previous one, have described the relationship between the detection rate and the level of the PSA, proving to be statistically significant (p=0.0001) and using as optimal cut-off point for the PSA a value of 2.43ng/ml.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> Others go further, detecting recurrences even with PSA≤1ng/ml (40% of their series).<a class="elsevierStyleCrossRef" href="#bib0145">29</a>The analysis of the PSA kinetics using as parameters the ascent rate and doubling time (PSAvel and PSAdt, respectively) may improve the selection of patients candidates for the technique.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> The PSA kinetics can reliably stratify the probability of success of the choline-PET/CT, the PSAdt being<6 months the most significant predictive factor and that better reflects the natural growth pattern of recurrent disease.<a class="elsevierStyleCrossRef" href="#bib0155">31</a>A review in which it is postulated that the choline-PET/CT may be the first diagnostic technique to be chosen for suspected recurrence, especially in cases of rapid kinetics, despite having a slight increase in the PSA<a class="elsevierStyleCrossRef" href="#bib0125">25</a> has recently been published. This hypothesis is endorsed by other studies showing that patients with positive PET/CT have a rapid kinetics (mean PSAdt: 6 months; mean PSAvel: 9.3ng/ml/year), being slow in negative scans (mean PSAdt: 15.4 months; mean PSAvel: 0.9ng/ml/year).<a class="elsevierStyleCrossRef" href="#bib0160">32</a> Schillaci et al., very close to the above findings, confirm the close relationship between the PSA kinetics and the detection of 18F-fluorocholine and recommend the technique in patients with PSAdt≤6 months and PSAvel>2ng/ml/year.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>Therapeutic implicationsWe assessed the usefulness of the choline-PET/CT as determining examination for the therapeutic strategy during the follow-up. The results are promising, because in 75 of the 156 patients analyzed (48%) in a recent retrospective study the therapeutic plan was modified based on the findings of the functional technique and assuming a major impact on the treatment strategy of recurrent PC.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> Other groups have analyzed the ability of the scan to differentiate local relapse and systemic, finding that 18F-fluorocholine favorably determines the therapeutic approach for each patient.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Following these observations, we believe that the distinction between local and systemic recurrence by choline-PET/CT can help in the selection of candidates for new therapies, being of particular interest in young patients where early institution of appropriate treatment can improve the quality of life.More and more people defend the usefulness of choline-PET/CT in programming the RT, even in patients who have received neoadjuvant hormone therapy (HT). 11C-choline determined a change in the extent of the target volume of the RT in 13% of the patients analyzed, in a retrospective study, in whom there was suspicion of recurrence after RP. Furthermore, 75% of the cases in which that volume increased, according to the findings of the PET/CT, remained free of disease during the follow-up time.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> Similarly 11F-fluorocholine behaves as a useful tool in the design of the irradiation field in patients with pelvic lymph nodes as recurrent disease.<a class="elsevierStyleCrossRef" href="#bib0180">36</a>Influence of hormone therapyThe presence of HT is an aspect that can affect the diagnostic accuracy of the technique, since the reduction in the choline uptake in response to a therapeutic androgen suppression appears to correlate with a reduction of the choline uptake.Fuccio et al., before a group of 14 patients with PSA increase after RP, evaluated the influence of hormonal manipulation on the detection of recurrences, conducting in all of them 2 PET/CT studies (before and 6 months after starting the HT). Their findings lean toward a marked reduction in the choline uptake and a decrease in the PSA during the time of HT, particularly in androgen-sensitive patients. The withdrawal of the HT prior to the study appears to increase the detection rate, the intensity of uptake of metastatic lesions and therefore the sensitivity of the test.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>In the same vein, the results of Giovacchini et al. support the conclusion that the HT with bicalutamide is associated with a significant decrease in the choline uptake in the gland, and confirm that this inhibition may also influence the uptake of lymph nodes or even bone. The influence of the HT makes them think that choline-PET/CT–in combination with the PSA– can be useful to assess the response to such treatment.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>These same authors, in a later work (2012), suggest that hormone-resistant patients with suspected biochemical failure are more likely to present a positive 11C-choline-PET/CT study.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> These reflections coincide with those of the Ceci group, since according to their results 11C-choline-PET/CT can detect recurrence in a substantial proportion of hormone-resistant patients, androgen withdrawal not being necessary whenever the PSA levels increase progressively and rapid kinetics is observed.<a class="elsevierStyleCrossRef" href="#bib0190">38</a>However, we observed some debate among some authors such as Henninger et al.<a class="elsevierStyleCrossRef" href="#bib0195">39</a> and the other groups. The data of Henninger determine that the technique has an acceptable diagnostic accuracy in the detection of recurrences in patients with HT, even when the PSA values are relatively low. Moreover, they found no statistically significant differences in the sensitivity of the 2 groups (with and without HT), in fact, the sensitivity in treatment group was superior (80 vs. 50% in the absence of HT).ConclusionsThe use of PET/CT with radiolabeled choline analogs provides promising results compared to 18F-FDG in PC.The choline is not useful in the primary location of the tumor, but it is in the identification of lymph node involvement in patients with newly diagnosed medium-high grade PC. Its main advantage over other imaging techniques in the detection of bone metastases is the ability to demonstrate the marrow infiltration early.The most important indication of the choline-PET/CT in PC is the detection of biochemical recurrence, conducting examination not being recommended when the values of this marker are <1ng/ml. Although the positivity of the test increases with the increase in the PSA value, it is more useful to conduct a study of the kinetics when selecting the patients candidate for examination.Finally, and although it is necessary to conduct studies with confirmatory data, the choline-PET/CT is emerging as a diagnostic tool that can provide new and interesting opportunities in the planning of the individualized treatment of PC.Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xres378209" "titulo" => array:4 [ 0 => "Abstract" 1 => "Introduction" 2 => "Evidence acquisition" 3 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec357262" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres378208" "titulo" => array:4 [ 0 => "Resumen" 1 => "Introducción" 2 => "Evidencia de adquisición" 3 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec357261" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Epidemiology" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Initial staging" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Biochemical recurrence" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Radiopharmaceuticals for positron emission tomography in prostate cancer" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Evidence of acquisition" ] 5 => array:3 [ "identificador" => "sec0035" "titulo" => "Evidence of synthesis" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0040" "titulo" => "Initial staging" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "T staging" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "N staging" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "M staging" ] ] ] ] ] 6 => array:3 [ "identificador" => "sec0060" "titulo" => "Biochemical recurrence" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Recurrente location" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Selection of patients" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Therapeutic implications" ] 3 => array:2 [ "identificador" => "sec0080" "titulo" => "Influence of hormone therapy" ] ] ] ] ] 5 => array:2 [ "identificador" => "sec0085" "titulo" => "Conclusions" ] 6 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-11-13" "fechaAceptado" => "2013-12-01" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec357262" "palabras" => array:6 [ 0 => "Prostate cancer" 1 => "Choline" 2 => "PET/CT" 3 => "Biochemical relapse" 4 => "Staging" 5 => "PSA kinetics" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec357261" "palabras" => array:6 [ 0 => "Cáncer de próstata" 1 => "Colina" 2 => "PET/TC" 3 => "Recurrencia bioquímica" 4 => "Estadificación" 5 => "Cinética PSA" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "IntroductionProstate cancer is the most frequent solid malignant tumor in Western countries. Positron emission tomography/X-ray computed tomography imaging with radiolabeled choline analogs is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. Evidence acquisitionA MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer» and «Choline-PET/CT». Other search terms were «Biochemical failure» and/or «Staging» and/or «PSA kinetics». English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. ConclusionsAccording to available data, radiolabeled choline analogs plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "IntroducciónEl cáncer de próstata es el tumor maligno sólido más frecuente en los países occidentales. La tomografía por emisión de positrones/tomografía computarizada con análogos radiomarcados de colina es una herramienta útil en la re-estadificación de pacientes con aumento del antígeno prostático específico después de tratamiento radical—donde las técnicas de imagen convencional tienen limitaciones importantes—así como en un seleccionado grupo de pacientes en la valoración inicial de esta neoplasia. Esta situación nos lleva a plantear una revisión de la literatura donde se evalúe la utilidad de esta exploración en la toma de decisiones diagnóstico-terapéuticas en el cáncer de próstata. Evidencia de adquisiciónRealizamos una búsqueda bibliográfica a través de la base de datos Medline (vía Pubmed) utilizando los términos Prostate cancer y Choline-PET/CT a los que añadimos los términos Biochemical failure y/o Staging y/o PSA kinetics. Así mismo, seleccionamos los trabajos en lengua inglesa y española e incluimos artículos originales, revisiones, revisiones sistemáticas, metaanálisis y guías de práctica clínica. ConclusionesDe acuerdo con los datos disponibles los análogos radiomarcados de colina desempeñan un papel importante en el manejo del cáncer de próstata, especialmente en la recurrencia bioquímica, donde la exactitud de la técnica se correlaciona bien con el valor del antígeno prostático específico y su cinética. Aunque esta técnica se perfila como una modalidad diagnóstica de aplicación en la planificación del tratamiento del cáncer de próstata, aún no se han realizado recomendaciones finales sobre su uso." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Navarro-Pelayo Láinez MM, Rodríguez-Fernández A, Gómez-Río M, Vázquez-Alonso F, Cózar-Olmo JM, Llamas-Elvira JM. Papel de la tomografía por emisión de positrones/tomografía computarizada con análogos radiomarcados de colina en el cáncer de próstata. Actas Urol Esp. 2014;38:613–621." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1072 "Ancho" => 1660 "Tamanyo" => 120914 ] ] "descripcion" => array:1 [ "en" => "Cell entrapment of 18F-FDG. After intravenous administration 18F-FDG is distributed by the circulatory system and incorporated into tumor cells by the same transport mechanisms as unlabeled glucose: sodium–glucose transporters and specific membrane transporters or GLUT. Glucose, in the cytoplasm, follows an enzymatic metabolism being phosphorylated by a hexokinase in glucose-6-phosphate, and subsequently by an isomerase is converted to fructose-6-phosphate. After this it can be transformed into glycogen or enter the glycolytic pathway. In the case of 18F-FDG, incorporating the fluorine atom prevents it from being metabolized after conversion to 18F-FDG-6-phosphate, consequently having a trapping inside the cell." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1493 "Ancho" => 1558 "Tamanyo" => 155042 ] ] "descripcion" => array:1 [ "en" => "Cell entrapment of radiolabeled choline analogs. The choline is introduced into the cell via specific transporters, and once inside it is phosphorylated by the enzyme choline-kinase to yield phosphocholine. This is the first step of the 3 that make up the enzyme cascade known as Kennedy pathway, whose final product is phosphatidylcholine or lecithin. Phosphatidylcholine—main membrane phospholipid—is synthesized in 2 steps by means of a reaction catalyzed by phosphocholine citidiltransferase and through phosphocholine transferase." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1399 "Ancho" => 1808 "Tamanyo" => 276901 ] ] "descripcion" => array:1 [ "en" => "73-Year-old patient with newly diagnosed prostate cancer (PSA: 11.95ng/ml; Gleason: 4+5; clinical stage: T3a) under study due to initial staging. 18F-fluorocholine-PET/CT examination shows in its axial sections of PET (A), CT (B), and fusion (F) a focal increase of uptake in the left lobe of the prostate gland (maxSUV: 6.72), compatible with the neoplastic activity already known at this location." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1149 "Ancho" => 2015 "Tamanyo" => 291344 ] ] "descripcion" => array:1 [ "en" => "75-Year-old patient diagnosed with prostate cancer: PSA 36; Gleason 4+5; T2b. (1) The axial cuts of the PET/CT with 18F-fluorocholine show in PET images (1A), CT (1B) and fusion (1C) significant hyper-uptake (maxSUV 4.62) in both prostatic lobes (empty arrow). (2) A deposit of the tracer in right internal iliac territory is also observed in the axial projections of the pelic cavity (2A–2C), with a maxSUV of 4.18, which corresponds to a small neoplastic aspect adenopathy (solid arrow)." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1384 "Ancho" => 1808 "Tamanyo" => 300294 ] ] "descripcion" => array:1 [ "en" => "64-Year-old patient with a history of prostatectomy 2 years ago. The axial cuts of PET images (A), CT (B), and fusion (C) of the study with 18F-fluorocholine show a hypermetabolic focus (maxSUV 3.29) at right inner para-iliac level (red arrow) coinciding with an unknown adenopathy of metastatic aspect at this location." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1056 "Ancho" => 1808 "Tamanyo" => 203781 ] ] "descripcion" => array:1 [ "en" => "70-Year-old patient with a history of prostate cancer treated with hormone therapy 3 years ago. During the follow-up a PET/CT is conducted with 18F-fluorocholine, due to progressive increase in the value of the PSA, which shows multiple bone hypermetabolic foci coinciding with metastatic aspect lesions distributed throughout the axial and appendicular skeleton. 1) The axial cuts of PET images (1A), CT (1B), and fusion (1C) show the existing uptake in both ilia, more striking on the right side, as well as significant uptake in the sacrum. 2) One can also appreciate various tracer deposits in the right scapula and cervical (C2) and dorsal column (D6 and D10) in PET coronal sections (2A), CT (2B), and fusion (2C)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical presentation, diagnosis, and staging of prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P.W. 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Review article

The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogs in prostate cancer

Papel de la tomografía por emisión de positrones/tomografía computarizada con análogos radiomarcados de colina en el cáncer de próstata

M.M. Navarro-Pelayo Láineza,

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mnavarropelayo@gmail.com

Corresponding author.

, A. Rodríguez-Fernándeza, M. Gómez-Ríoa, F. Vázquez-Alonsob, J.M. Cózar-Olmob, J.M. Llamas-Elviraa

a Servicio de Medicina Nuclear, Hospital Universitario Virgen de las Nieves, Granada, Spain

b Servicio de Urología, Hospital Universitario Virgen de las Nieves, Granada, Spain

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definitive diagnosis is based on the presence of adenocarcinoma in the prostate biopsy&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Initial staging</span><p id="par0015" class="elsevierStylePara elsevierViewall">Local staging &#40;T staging&#41; of PC is based on the results of TR and MR&#46; Possibly the latter is the technique of choice for the correct delimitation of its extension&#44; as the new techniques&#8212;endorectal coils&#44; spectroscopy&#44; and combination of MR with dynamic contrast and enhanced MR in T2&#8212;offer better results in terms of PC staging&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The nodal status &#40;N staging&#41; is especially important when a potentially curative treatment is expected&#46; Conventional imaging tests have limitations in detection of metastases &#60;5<span class="elsevierStyleHsp" style=""></span>mm&#44; so that the pelvic lymphadenectomy remains the most reliable method&#59; however&#44; it is still a controversial and invasive procedure with regard to the most appropriate technique to perform &#40;standard or extended&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Metastatic bone site is the most frequent in PC&#44; and the best way to evaluate it is the bone scan&#44; which has traditionally shown a high sensitivity&#46; In contrast&#44; it seems not to be indicated in asymptomatic patients when the serum PSA concentration is &#60;20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml in well or moderately differentiated tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Biochemical recurrence</span><p id="par0030" class="elsevierStylePara elsevierViewall">Tumor recurrence is an event that occurs in 20&#8211;50&#37; of patients after radical prostatectomy &#40;RP&#41; and in more than 30&#8211;40&#37; of those who received external beam radiotherapy &#40;RT&#41;&#46; After a RP&#44; only 2 consecutive values &#62;0&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml represent a recurrent cancer&#46; However&#44; the failure of RT has been redefined several times&#44; now being known as PSA elevation&#62;2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml above the PSA nadir&#46; There is no consensus for the other treatments&#8212;cryotherapy or brachytherapy&#8212;and therefore it is not possible to give definite recommendations on biochemical failure in these cases&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Only the PSA concentration and&#44; ultimately&#44; the RT are the only tests to routinely be performed during the follow-up&#46; The identification and precise localization of recurrences has not yet been achieved&#46; CT has a low sensitivity and specificity in this context&#44; particularly if the size of the recurrence is &#60;2<span class="elsevierStyleHsp" style=""></span>cm&#46; For its part&#44; the MR is not a first-line diagnostic tool either&#44; although some authors suggest that the incorporation of endorectal coils makes it a sensitive and predictive technique in identifying recurrence after RP&#46; Bone scintigraphy is indicated in the control of symptomatic patients&#44; but we must remember that its low specificity sometimes determines the performance of additional examinations to verify the findings&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Radiopharmaceuticals for positron emission tomography in prostate cancer</span><p id="par0040" class="elsevierStylePara elsevierViewall">The multimodal technique positron emission tomography&#47;computed tomography &#40;PET&#47;CT&#41;&#44; which combines the performance of the anatomical and functional scans&#44; is emerging as a diagnostic tool useful in the study of PC&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Although the most widely used radiopharmaceutical is 2-&#91;<span class="elsevierStyleSup">18</span>F&#93;fluoro-2-deoxy-<span class="elsevierStyleSmallCaps">d</span>-glucose &#40;<span class="elsevierStyleSup">18</span>F-FDG&#41;&#44; it is not routinely used in PC&#46; Affinity for the carbohydrate tracer is related to the glucose transporter expression of the membrane &#40;GLUT-1&#41;&#44; present in greater amount in the poorly differentiated hormone-independent cell lines than in well-differentiated hormone-sensitive ones&#46; The lower uptake of <span class="elsevierStyleSup">18</span>F-FDG in PC&#44; compared with other tumors&#44; has been attributed to the fact that this malignancy has a slower metabolism and a lower expression of GLUT-1<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> transporters &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Physiological uptake of <span class="elsevierStyleSup">18</span>F-FDG is observed in viable tissues such as the brain&#44; myocardium&#44; liver&#44; gastrointestinal tract&#44; muscle&#44; and bone marrow&#46; Urinary excretion of the tracer is an added factor that reduces the efficiency of the technique&#44; since the intense activity in ureters and bladder can mask injuries in the prostate and surrounding tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">There is currently great interest in choline analogs&#46; Choline is introduced into the cell via specific transporters&#44; and once inside it is phosphorylated by the enzyme choline-kinase &#40;CK&#41; to yield phosphocholine&#46; This is the first step of the 3 that make up the so-called Kennedy pathway &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; enzymatic cascade&#44; whose final product is phosphatidylcholine or lecithin&#46; Phosphatidylcholine&#44; the main membrane phospholipid&#44; is synthesized in 2 steps by means of a catalyzed reaction by phosphocholine citidiltransferase and through phosphocholine transferase&#46; Although the specific mechanism by which the tracer uptake is produced is not sufficiently clarified&#44; it seems to be due to 2 situations that occur in proliferative processes&#58; increase in the transport and in the phosphorylation of choline&#8212;primarily due to the overexpression of CK&#8212;as well as increased need for lipid formation&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">No major differences were found in the biodistribution of the choline&#44; regardless of the isotope that it is marked with &#40;<span class="elsevierStyleSup">11</span>C or <span class="elsevierStyleSup">18</span>F&#41;&#44; except for physiological urinary elimination which is higher with <span class="elsevierStyleSup">18</span>F-fluorocholine&#46; Under normal conditions we can find an intense tracer uptake in the liver and pancreas&#44; being somewhat lower in the spleen&#44; salivary and lacrimal glands&#46; Tracer deposits in both kidneys&#44; ureters and bladder are considered equally physiological distribution&#46; Other less common locations but also described are the bone marrow &#40;dorsal vertebral level&#41; and the intestinal tract due to the high proliferation of the mucosa at this level &#40;especially important in the small intestine&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">11</span>C-choline is indistinguishable from the natural molecule of choline&#59; however&#44; its short half-life &#40;20<span class="elsevierStyleHsp" style=""></span>min&#41; causes frequent logistical problems&#44; since it forces to work in a center near a cyclotron&#46; Thus&#44; it is important to have radiopharmaceuticals with greater half life as <span class="elsevierStyleSup">18</span>F-fluorocholine &#40;110<span class="elsevierStyleHsp" style=""></span>min&#41; that can be transported to centers away from the producer cyclotron&#46; The increased urinary excretion of <span class="elsevierStyleSup">18</span>F-fluorocholine&#44; as explained&#44; can alter the results of the image in the pelvis&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The present review aims to critically analyze the current evidence for the use of <span class="elsevierStyleSup">11</span>C and <span class="elsevierStyleSup">18</span>F-choline-PET&#47;CT in staging and suspected biochemical failure after treatment of PC&#44; as well as its role as a diagnostic tool in treatment strategies during follow-up&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Evidence of acquisition</span><p id="par0075" class="elsevierStylePara elsevierViewall">To select the bibliography used in the drafting of this article a thorough search was conducted in the scientific literature using the Medline database &#40;via Pubmed&#41;&#46; Relevant publications were collected by means of the inclusion of the following keywords</p><p id="par0080" class="elsevierStylePara elsevierViewall">Prostate cancer and Choline-PET&#44; to which we added the terms Biochemical failure and&#47;or Staging and&#47;or PSA kinetics&#44; arranged in different combinations&#46; Similarly&#44; we selected and critically reviewed the works in English and Spanish language published between 2008 and 2013&#46; Original articles&#44; reviews&#44; systematic reviews&#44; meta-analyses&#44; and clinical practice guidelines were included&#46; The studies published only as an abstract or the reports of the meetings were not taken into account&#46; In general&#44; the original ratio of bibliographic citations was discussed with all the authors to select the most relevant articles&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Evidence of synthesis</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Initial staging</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">T staging</span><p id="par0085" class="elsevierStylePara elsevierViewall">So far choline-PET&#47;CT is not a first-line diagnostic tool in the location of the primary tumor in patients with newly diagnosed PC&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In this neoplasia&#44; the presence of multiple foci of tumor is characteristic-most small-difficult to detect by PET&#47;CT&#44; especially those with mild uptake and size &#60;5<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Moreover&#44; its limited ability to distinguish between tumor tissue and benign prostatic diseases with affinity for the tracer &#40;prostatitis and benign prostatic hypertrophy&#41; often involves a high number of false positives&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Because of these limitations&#44; some groups have made technological innovations that make it possible to improve the results&#46; The &#8216;double phase&#8217; image acquisition &#40;with late projections at 90<span class="elsevierStyleHsp" style=""></span>min postinjection&#41; enables us to differentiate between benign and malignant tissue&#44; since over time the uptake of neoplastic lesions remains stable or even increases&#44; decreasing in benign areas&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">An application of choline-PET&#47;CT that increasingly becomes stronger is the location of the tumor focus in cases of high clinical suspicion of PC and at least 2 negative biopsies<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> in order to properly guide a new biopsy and increase the rate of detection<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">N staging</span><p id="par0100" class="elsevierStylePara elsevierViewall">The choline-PET&#47;CT is a reliable and non-invasive technique for nodal staging in patients with medium-high risk according to the D&#8217;Amico classification&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> especially if we consider that conventional imaging modalities have limitations in this context&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> However&#44; the bowel activity and physiological excretion in the urinary system &#40;shown in the <span class="elsevierStyleSup">18</span>F-fluorocholine&#41;&#44; along with the frequent uptake in inflammatory nodes&#44; may interfere with the identification of the possible lymph node involvement&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Most analyzed studies show high specificity but low sensitivity among their results&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;14</span></a> In a recent systematic review&#44; values of sensitivity&#44; specificity&#44; positive predictive value &#40;PPV&#41;&#44; and negative predictive value &#40;NPV&#41; of 66&#44; 96&#44; 82 and 92&#37; respectively in the assessment of lymph nodes size &#62;5<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Therefore&#44; the choline can be useful for detecting metastatic nodal lesions of diameter &#8805;5<span class="elsevierStyleHsp" style=""></span>mm&#44; especially when dynamic acquisition or &#8220;dual stage&#8221;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41; is performed&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">M staging</span><p id="par0110" class="elsevierStylePara elsevierViewall">The results about the usefulness of the choline-PET&#47;CT in M staging are consistent&#58; it is a useful technique to rule out distant metastases in patients at high risk candidates for surgical treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Hodolic et al&#46; state that the sensitivity&#44; specificity&#44; and diagnostic accuracy of <span class="elsevierStyleSup">18</span>F-fluorocholine in detecting bone metastases is 74&#46;99 and 85&#37;&#44; respectively&#59; moreover&#44; they coincide with Beheshti et al&#46; that the technique appears to be superior to bone scintigraphy by demonstrating the marrow infiltration early&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In a recent cohort study <span class="elsevierStyleSup">18</span>F-fluorocholine modified the therapeutic approach in 20&#37; of the patients&#44; as it evidenced bone metastatic spread in patients with negative or inconclusive bone scintigraphy&#44; assuming the change of therapy with curative intent to palliative&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Again&#44; performing delayed images is of great importance by increasing the sensitivity in the detection of bone metastases&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></span></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Biochemical recurrence</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Recurrente location</span><p id="par0125" class="elsevierStylePara elsevierViewall">As shown in the literature&#44; the usefulness of choline-PET&#47;CT is clear in the detection of recurrence after RP&#44; as well as the relationship with the value of the PSA&#46; In fact&#44; in the work by Breeuwsma et al&#46; it is stated that a negative <span class="elsevierStyleSup">11</span>C-choline-PET&#47;CT correlates with a high disease-free survival and ensures reduced need for treatment in patients with suspected recurrence after RP&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> With a threshold of standard uptake value &#40;maxSUV&#41;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3 and a size of tumor focus &#62;1&#46;7<span class="elsevierStyleHsp" style=""></span>cm&#44; the sensitivity and specificity of <span class="elsevierStyleSup">11</span>C-choline in local recurrence after RP is 73 and 88&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Only in a recently published study that compared MRI with contrast and spectroscopy and <span class="elsevierStyleSup">18</span>F-fluorocholine-PET&#47;CT in patients with elevation of the PSA after RP&#44; the sensitivity of MRI is superior to that of PET in local recurrences &#60;10<span class="elsevierStyleHsp" style=""></span>mm&#44; with similar results in &#62;10<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The same cannot be said after RT&#44; the presence of inflammatory tissue after treatment being frequent with affinity for the radiopharmaceutical&#46; Therefore&#44; we can not make reliable final recommendations in these patients&#44; especially if we take into account the scarcity of published studies about it&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The choline-PET&#47;CT has a high PPV &#40;86&#37;&#41; in the identification and location of nodal recurrence after radical treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46; However&#44; in the analysis per lesions the NPVis low&#44; since it is not capable of detecting microscopic disease &#40;the mean diameter of the true positives is 15<span class="elsevierStyleHsp" style=""></span>mm&#44; while that of false negatives is 6&#46;3<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> It is important to mention that we must be cautious in the evaluation of mediastinal lymph nodes&#44; where the presence of inflammatory&#47;reactive uptake is frequent&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">There are studies that have compared the bone scintigraphy and PET&#47;CT with choline during the follow-up of patients with previously treated PC&#46; Most authors are inclined to choline analogs&#44; showing an early assessment and a higher overall sensitivity in detecting bone metastases &#40;30 lesions with <span class="elsevierStyleSup">11</span>C-choline were observed&#44; not suspected by the scintigraphy&#44; in 14&#46;6&#37; of the patients analyzed in the study by Fuccio et al&#46;&#41;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46; The results of another retrospective study showed a higher specificity and PPV of <span class="elsevierStyleSup">11</span>C-choline on bone scintigraphy&#44; being so that a positive result at the bone level is reliably considered by the authors as a malignant lesion&#44; even in the absence of confirmatory scans&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Selection of patients</span><p id="par0145" class="elsevierStylePara elsevierViewall">None of the risk factors for recurrence known&#8212;patient age &#40;&#62;65 years&#41;&#44; time between surgery and relapse&#44; previous biochemical failure&#44; Gleason score&#44; initial T and N stages&#8212;seems to influence the sensitivity of the test as the PSA value does&#46; However&#44; all these variables can be useful for the specialist&#44; helping to select candidates for conducting examination&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The authors assume that the higher the PSA value&#44; the greater the tissue metabolism&#44; and therefore the greater the avidity for <span class="elsevierStyleSup">18</span>F-fluorocholine&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> increasing the ability to detect recurrences&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However&#44; in those cases where the increase of the PSA is very discreet&#44; positive results must be validated with other techniques&#44; taking into account that the specificity and PPV of <span class="elsevierStyleSup">18</span>F-fluorocholine-PET&#47;CT decrease with low PSA values&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">If we analyze the works published to date&#44; we will realize that there is no consensus about the ideal cut-off point for the PSA value&#46; For their part&#44; Krause et al&#46; found a linear relationship between the value of the PSA and the positive results of the PET&#47;CT&#58; 36&#37; of the studies with PSA<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; 43&#37; with 1<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>PSA<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; 62&#37; with 2<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>PSA<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; and 73&#37; with PSA<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Other works&#44; like the previous one&#44; have described the relationship between the detection rate and the level of the PSA&#44; proving to be statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; and using as optimal cut-off point for the PSA a value of 2&#46;43<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Others go further&#44; detecting recurrences even with PSA<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;40&#37; of their series&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The analysis of the PSA kinetics using as parameters the ascent rate and doubling time &#40;PSAvel and PSAdt&#44; respectively&#41; may improve the selection of patients candidates for the technique&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> The PSA kinetics can reliably stratify the probability of success of the choline-PET&#47;CT&#44; the PSAdt being<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>6 months the most significant predictive factor and that better reflects the natural growth pattern of recurrent disease&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">A review in which it is postulated that the choline-PET&#47;CT may be the first diagnostic technique to be chosen for suspected recurrence&#44; especially in cases of rapid kinetics&#44; despite having a slight increase in the PSA<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> has recently been published&#46; This hypothesis is endorsed by other studies showing that patients with positive PET&#47;CT have a rapid kinetics &#40;mean PSAdt&#58; 6 months&#59; mean PSAvel&#58; 9&#46;3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#47;year&#41;&#44; being slow in negative scans &#40;mean PSAdt&#58; 15&#46;4 months&#59; mean PSAvel&#58; 0&#46;9<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#47;year&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Schillaci et al&#46;&#44; very close to the above findings&#44; confirm the close relationship between the PSA kinetics and the detection of <span class="elsevierStyleSup">18</span>F-fluorocholine and recommend the technique in patients with PSAdt<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>6 months and PSAvel<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#47;year&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Therapeutic implications</span><p id="par0170" class="elsevierStylePara elsevierViewall">We assessed the usefulness of the choline-PET&#47;CT as determining examination for the therapeutic strategy during the follow-up&#46; The results are promising&#44; because in 75 of the 156 patients analyzed &#40;48&#37;&#41; in a recent retrospective study the therapeutic plan was modified based on the findings of the functional technique and assuming a major impact on the treatment strategy of recurrent PC&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Other groups have analyzed the ability of the scan to differentiate local relapse and systemic&#44; finding that <span class="elsevierStyleSup">18</span>F-fluorocholine favorably determines the therapeutic approach for each patient&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Following these observations&#44; we believe that the distinction between local and systemic recurrence by choline-PET&#47;CT can help in the selection of candidates for new therapies&#44; being of particular interest in young patients where early institution of appropriate treatment can improve the quality of life&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">More and more people defend the usefulness of choline-PET&#47;CT in programming the RT&#44; even in patients who have received neoadjuvant hormone therapy &#40;HT&#41;&#46; <span class="elsevierStyleSup">11</span>C-choline determined a change in the extent of the target volume of the RT in 13&#37; of the patients analyzed&#44; in a retrospective study&#44; in whom there was suspicion of recurrence after RP&#46; Furthermore&#44; 75&#37; of the cases in which that volume increased&#44; according to the findings of the PET&#47;CT&#44; remained free of disease during the follow-up time&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Similarly <span class="elsevierStyleSup">11</span>F-fluorocholine behaves as a useful tool in the design of the irradiation field in patients with pelvic lymph nodes as recurrent disease&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Influence of hormone therapy</span><p id="par0180" class="elsevierStylePara elsevierViewall">The presence of HT is an aspect that can affect the diagnostic accuracy of the technique&#44; since the reduction in the choline uptake in response to a therapeutic androgen suppression appears to correlate with a reduction of the choline uptake&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Fuccio et al&#46;&#44; before a group of 14 patients with PSA increase after RP&#44; evaluated the influence of hormonal manipulation on the detection of recurrences&#44; conducting in all of them 2 PET&#47;CT studies &#40;before and 6 months after starting the HT&#41;&#46; Their findings lean toward a marked reduction in the choline uptake and a decrease in the PSA during the time of HT&#44; particularly in androgen-sensitive patients&#46; The withdrawal of the HT prior to the study appears to increase the detection rate&#44; the intensity of uptake of metastatic lesions and therefore the sensitivity of the test&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">In the same vein&#44; the results of Giovacchini et al&#46; support the conclusion that the HT with bicalutamide is associated with a significant decrease in the choline uptake in the gland&#44; and confirm that this inhibition may also influence the uptake of lymph nodes or even bone&#46; The influence of the HT makes them think that choline-PET&#47;CT&#8211;in combination with the PSA&#8211; can be useful to assess the response to such treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">These same authors&#44; in a later work &#40;2012&#41;&#44; suggest that hormone-resistant patients with suspected biochemical failure are more likely to present a positive <span class="elsevierStyleSup">11</span>C-choline-PET&#47;CT study&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> These reflections coincide with those of the Ceci group&#44; since according to their results <span class="elsevierStyleSup">11</span>C-choline-PET&#47;CT can detect recurrence in a substantial proportion of hormone-resistant patients&#44; androgen withdrawal not being necessary whenever the PSA levels increase progressively and rapid kinetics is observed&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">However&#44; we observed some debate among some authors such as Henninger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> and the other groups&#46; The data of Henninger determine that the technique has an acceptable diagnostic accuracy in the detection of recurrences in patients with HT&#44; even when the PSA values are relatively low&#46; Moreover&#44; they found no statistically significant differences in the sensitivity of the 2 groups &#40;with and without HT&#41;&#44; in fact&#44; the sensitivity in treatment group was superior &#40;80 vs&#46; 50&#37; in the absence of HT&#41;&#46;</p></span></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conclusions</span><p id="par0205" class="elsevierStylePara elsevierViewall">The use of PET&#47;CT with radiolabeled choline analogs provides promising results compared to <span class="elsevierStyleSup">18</span>F-FDG in PC&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">The choline is not useful in the primary location of the tumor&#44; but it is in the identification of lymph node involvement in patients with newly diagnosed medium-high grade PC&#46; Its main advantage over other imaging techniques in the detection of bone metastases is the ability to demonstrate the marrow infiltration early&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The most important indication of the choline-PET&#47;CT in PC is the detection of biochemical recurrence&#44; conducting examination not being recommended when the values of this marker are &#60;1<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; Although the positivity of the test increases with the increase in the PSA value&#44; it is more useful to conduct a study of the kinetics when selecting the patients candidate for examination&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Finally&#44; and although it is necessary to conduct studies with confirmatory data&#44; the choline-PET&#47;CT is emerging as a diagnostic tool that can provide new and interesting opportunities in the planning of the individualized treatment of PC&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflict of interest</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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            6 => array:3 [
              "identificador" => "sec0060"
              "titulo" => "Biochemical recurrence"
              "secciones" => array:4 [
                0 => array:2 [
                  "identificador" => "sec0065"
                  "titulo" => "Recurrente location"
                ]
                1 => array:2 [
                  "identificador" => "sec0070"
                  "titulo" => "Selection of patients"
                ]
                2 => array:2 [
                  "identificador" => "sec0075"
                  "titulo" => "Therapeutic implications"
                ]
                3 => array:2 [
                  "identificador" => "sec0080"
                  "titulo" => "Influence of hormone therapy"
                ]
              ]
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          ]
        ]
        5 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conclusions"
        ]
        6 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Conflict of interest"
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        7 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-11-13"
    "fechaAceptado" => "2013-12-01"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec357262"
          "palabras" => array:6 [
            0 => "Prostate cancer"
            1 => "Choline"
            2 => "PET&#47;CT"
            3 => "Biochemical relapse"
            4 => "Staging"
            5 => "PSA kinetics"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec357261"
          "palabras" => array:6 [
            0 => "C&#225;ncer de pr&#243;stata"
            1 => "Colina"
            2 => "PET&#47;TC"
            3 => "Recurrencia bioqu&#237;mica"
            4 => "Estadificaci&#243;n"
            5 => "Cin&#233;tica PSA"
          ]
        ]
      ]
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Prostate cancer is the most frequent solid malignant tumor in Western countries&#46; Positron emission tomography&#47;X-ray computed tomography imaging with radiolabeled choline analogs is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment &#40;in whom conventional imaging techniques have important limitations&#41; as well as in the initial assessment of a selected group of prostate cancer patients&#46; For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Evidence acquisition</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A MEDLINE &#40;PubMed way&#41; literature search was performed using the search parameters&#58; &#171;Prostate cancer&#187; and &#171;Choline-PET&#47;CT&#187;&#46; Other search terms were &#171;Biochemical failure&#187; and&#47;or &#171;Staging&#187; and&#47;or &#171;PSA kinetics&#187;&#46; English and Spanish papers were selected&#59; original articles&#44; reviews&#44; systematic reviews and clinical guidelines were included&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Conclusions</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">According to available data&#44; radiolabeled choline analogs plays an important role in the management of prostate cancer&#44; especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics&#46; Although is an emerging diagnostic technique useful in treatment planning of prostate cancer&#44; final recommendations have not been submitted&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0030">Introducci&#243;n</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El c&#225;ncer de pr&#243;stata es el tumor maligno s&#243;lido m&#225;s frecuente en los pa&#237;ses occidentales&#46; La tomograf&#237;a por emisi&#243;n de positrones&#47;tomograf&#237;a computarizada con an&#225;logos radiomarcados de colina es una herramienta &#250;til en la re-estadificaci&#243;n de pacientes con aumento del ant&#237;geno prost&#225;tico espec&#237;fico despu&#233;s de tratamiento radical&#8212;donde las t&#233;cnicas de imagen convencional tienen limitaciones importantes&#8212;as&#237; como en un seleccionado grupo de pacientes en la valoraci&#243;n inicial de esta neoplasia&#46; Esta situaci&#243;n nos lleva a plantear una revisi&#243;n de la literatura donde se eval&#250;e la utilidad de esta exploraci&#243;n en la toma de decisiones diagn&#243;stico-terap&#233;uticas en el c&#225;ncer de pr&#243;stata&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0035">Evidencia de adquisici&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Realizamos una b&#250;squeda bibliogr&#225;fica a trav&#233;s de la base de datos Medline &#40;v&#237;a Pubmed&#41; utilizando los t&#233;rminos <span class="elsevierStyleItalic">Prostate cancer</span> y <span class="elsevierStyleItalic">Choline-PET&#47;CT</span> a los que a&#241;adimos los t&#233;rminos <span class="elsevierStyleItalic">Biochemical failure</span> y&#47;o <span class="elsevierStyleItalic">Staging</span> y&#47;o <span class="elsevierStyleItalic">PSA kinetics</span>&#46; As&#237; mismo&#44; seleccionamos los trabajos en lengua inglesa y espa&#241;ola e incluimos art&#237;culos originales&#44; revisiones&#44; revisiones sistem&#225;ticas&#44; metaan&#225;lisis y gu&#237;as de pr&#225;ctica cl&#237;nica&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">Conclusiones</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">De acuerdo con los datos disponibles los an&#225;logos radiomarcados de colina desempe&#241;an un papel importante en el manejo del c&#225;ncer de pr&#243;stata&#44; especialmente en la recurrencia bioqu&#237;mica&#44; donde la exactitud de la t&#233;cnica se correlaciona bien con el valor del ant&#237;geno prost&#225;tico espec&#237;fico y su cin&#233;tica&#46; Aunque esta t&#233;cnica se perfila como una modalidad diagn&#243;stica de aplicaci&#243;n en la planificaci&#243;n del tratamiento del c&#225;ncer de pr&#243;stata&#44; a&#250;n no se han realizado recomendaciones finales sobre su uso&#46;</p>"
      ]
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    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Navarro-Pelayo L&#225;inez MM&#44; Rodr&#237;guez-Fern&#225;ndez A&#44; G&#243;mez-R&#237;o M&#44; V&#225;zquez-Alonso F&#44; C&#243;zar-Olmo JM&#44; Llamas-Elvira JM&#46; Papel de la tomograf&#237;a por emisi&#243;n de positrones&#47;tomograf&#237;a computarizada con an&#225;logos radiomarcados de colina en el c&#225;ncer de pr&#243;stata&#46; Actas Urol Esp&#46; 2014&#59;38&#58;613&#8211;621&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Cell entrapment of <span class="elsevierStyleSup">18</span>F-FDG&#46; After intravenous administration <span class="elsevierStyleSup">18</span>F-FDG is distributed by the circulatory system and incorporated into tumor cells by the same transport mechanisms as unlabeled glucose&#58; sodium&#8211;glucose transporters and specific membrane transporters or GLUT&#46; Glucose&#44; in the cytoplasm&#44; follows an enzymatic metabolism being phosphorylated by a hexokinase in glucose-6-phosphate&#44; and subsequently by an isomerase is converted to fructose-6-phosphate&#46; After this it can be transformed into glycogen or enter the glycolytic pathway&#46; In the case of <span class="elsevierStyleSup">18</span>F-FDG&#44; incorporating the fluorine atom prevents it from being metabolized after conversion to <span class="elsevierStyleSup">18</span>F-FDG-6-phosphate&#44; consequently having a trapping inside the cell&#46;</p>"
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Cell entrapment of radiolabeled choline analogs&#46; The choline is introduced into the cell via specific transporters&#44; and once inside it is phosphorylated by the enzyme choline-kinase to yield phosphocholine&#46; This is the first step of the 3 that make up the enzyme cascade known as Kennedy pathway&#44; whose final product is phosphatidylcholine or lecithin&#46; Phosphatidylcholine&#8212;main membrane phospholipid&#8212;is synthesized in 2 steps by means of a reaction catalyzed by phosphocholine citidiltransferase and through phosphocholine transferase&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">73-Year-old patient with newly diagnosed prostate cancer &#40;PSA&#58; 11&#46;95<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; Gleason&#58; 4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>5&#59; clinical stage&#58; T3a&#41; under study due to initial staging&#46; <span class="elsevierStyleSup">18</span>F-fluorocholine-PET&#47;CT examination shows in its axial sections of PET &#40;A&#41;&#44; CT &#40;B&#41;&#44; and fusion &#40;F&#41; a focal increase of uptake in the left lobe of the prostate gland &#40;maxSUV&#58; 6&#46;72&#41;&#44; compatible with the neoplastic activity already known at this location&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">75-Year-old patient diagnosed with prostate cancer&#58; PSA 36&#59; Gleason 4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>5&#59; T2b&#46; &#40;1&#41; The axial cuts of the PET&#47;CT with <span class="elsevierStyleSup">18</span>F-fluorocholine show in PET images &#40;1A&#41;&#44; CT &#40;1B&#41; and fusion &#40;1C&#41; significant hyper-uptake &#40;maxSUV 4&#46;62&#41; in both prostatic lobes &#40;empty arrow&#41;&#46; &#40;2&#41; A deposit of the tracer in right internal iliac territory is also observed in the axial projections of the pelic cavity &#40;2A&#8211;2C&#41;&#44; with a maxSUV of 4&#46;18&#44; which corresponds to a small neoplastic aspect adenopathy &#40;solid arrow&#41;&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">64-Year-old patient with a history of prostatectomy 2 years ago&#46; The axial cuts of PET images &#40;A&#41;&#44; CT &#40;B&#41;&#44; and fusion &#40;C&#41; of the study with <span class="elsevierStyleSup">18</span>F-fluorocholine show a hypermetabolic focus &#40;maxSUV 3&#46;29&#41; at right inner para-iliac level &#40;red arrow&#41; coinciding with an unknown adenopathy of metastatic aspect at this location&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">70-Year-old patient with a history of prostate cancer treated with hormone therapy 3 years ago&#46; During the follow-up a PET&#47;CT is conducted with <span class="elsevierStyleSup">18</span>F-fluorocholine&#44; due to progressive increase in the value of the PSA&#44; which shows multiple bone hypermetabolic foci coinciding with metastatic aspect lesions distributed throughout the axial and appendicular skeleton&#46; 1&#41; The axial cuts of PET images &#40;1A&#41;&#44; CT &#40;1B&#41;&#44; and fusion &#40;1C&#41; show the existing uptake in both ilia&#44; more striking on the right side&#44; as well as significant uptake in the sacrum&#46; 2&#41; One can also appreciate various tracer deposits in the right scapula and cervical &#40;C2&#41; and dorsal column &#40;D6 and D10&#41; in PET coronal sections &#40;2A&#41;&#44; CT &#40;2B&#41;&#44; and fusion &#40;2C&#41;&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:39 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical presentation&#44; diagnosis&#44; and staging of prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P&#46;W&#46; Kantoff"
                            1 => "M&#46;E&#46; Taplin"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "UpToDate"
                        "fecha" => "2011"
                      ]
                    ]
                  ]
                ]
              ]
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              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "<span class="elsevierStyleSup">18</span>F-fluorocholine for prostate cancer imaging&#58; a systematic review of the literature"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "G&#46; Bauman"
                            1 => "T&#46; Belhocine"
                            2 => "M&#46; Kovacs"
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                            4 => "M&#46; Beheshti"
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                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/pcan.2011.35"
                      "Revista" => array:6 [
                        "tituloSerie" => "Prostate Cancer Prostatic Dis"
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                        "volumen" => "15"
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              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Heidenreich"
                            1 => "M&#46; Bolla"
                            2 => "S&#46; Joniau"
                            3 => "M&#46;D&#46; Mason"
                            4 => "V&#46; Matveev"
                            5 => "N&#46; Mottet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:2 [
                        "titulo" => "European Association of Urology 2010&#46; Guidelines on prostate cancer"
                        "serieFecha" => "2014"
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            3 => array:3 [
              "identificador" => "bib0020"
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                      "titulo" => "<span class="elsevierStyleSup">18</span>F-choline PET&#47;CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease&#58; a prospective study of 130 patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Beheshti"
                            1 => "L&#46; Imamovic"
                            2 => "G&#46; Broinger"
                            3 => "R&#46; Vali"
                            4 => "P&#46; Waldenberger"
                            5 => "F&#46; Stoiber"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1148/radiol.09090413"
                      "Revista" => array:6 [
                        "tituloSerie" => "Radiology"
                        "fecha" => "2010"
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                          ]
                        ]
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              "identificador" => "bib0025"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Pelosi"
                            1 => "V&#46; Arena"
                            2 => "A&#46; Skanjeti"
                            3 => "V&#46; Pirro"
                            4 => "A&#46; Douroukas"
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                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
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                      "titulo" => "The role of PET&#47;computed tomography scan in the management of prostate cancer"
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                          "etal" => false
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                          ]
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                        "fecha" => "2011"
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                      "titulo" => "Update on the use of radiopharmaceuticals for positron emission tomography imaging of prostate cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "J&#46;R&#46; Garc&#237;a"
                          ]
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                        "fecha" => "2013"
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Article information

ISSN: 21735786
Original language: English

DOI:10.1016/j.acuroe.2014.04.004

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2016 February	0	3	3
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2015 October	0	1	1
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2015 July	0	1	1
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