Original Article
Radiation exposure of the operators in the preparation and administration of yttrium-90 microspheres in the treatment of malignant hepatic lesions: What is the risk?
Exposición a la radiación de los operadores en la preparación y administración de microesferas de itrio-90 en el tratamiento de lesiones hepáticas malignas: ¿cuál es el riesgo?
Teresa Scotognella, Andrea Morasca, Luca Zagaria, Amedeo Capostosti, Roberto Iezzi, Luca Indovina, Alessandro Giordano, Germano Perotti
Fondazione Policlinico, Universitario Agostino Gemelli IRCSS, Italy
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MIP (A) of patient with fever of unknown origin and Sjögren syndrome receiving treatment with rituximab. Clinical picture compatible with COVID-19 (fever and CT with bilateral parenchymatous involvement) since March 25, 2020 with 3 PCR-negative nasopharyngeal exudates. PET/CT 1 month later showing intense bilateral pulmonary uptake coinciding with radiological alterations visible in the axial CT (B) and PET/CT slices (C) and probable medullary reactivation. A posterior bronchoaspirate was performed confirming persistent infection by SARS-CoV-2 in the PCR.</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Case 2. MIP (A) of patient with multiple sclerosis receiving treatment with rituximab and post-COVID fever of 2 months of evolution. Pathological uptake of elevated intensity is observed in both pulmonary parenchymas coinciding with areas of opacification in the CT and PET/CT (B,C). A transbronchial biopsy was later performed showing T lymphocyte pneumonitis (D), and immunohistochemical staining showed the persistence of SARS-CoV-2 in lung tissue. (E).</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Case 3. MIP (A) of young patient with no history of interest with post-COVID dsypnea of 8 months of evolution. Multiple nodular uptakes are shown in both lungs and bilateral hilar mediastinal uptake, coinciding with areas of opacification of the parenchyma and adenopathies which were not increased in size (B, C). The histological lymph node study obtained by echobronchoscopy (D) showed non necrotizing sarcoid type granulomatous inflammation. The posterior transbronchial biopsy showed the same type of granulomatous inflammation without the presence of virus in the immunostaining.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "B. Rodríguez-Alfonso, S. Ruiz Solís, L. Silva-Hernández, I. Pintos Pascual, S. Aguado Ibáñez, C. Salas Antón" "autores" => array:6 [ 0 => array:2 [ "nombre" => "B." "apellidos" => "Rodríguez-Alfonso" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Ruiz Solís" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Silva-Hernández" ] 3 => array:2 [ "nombre" => "I." "apellidos" => "Pintos Pascual" ] 4 => array:2 [ "nombre" => "S." "apellidos" => "Aguado Ibáñez" ] 5 => array:2 [ "nombre" => "C." "apellidos" => "Salas Antón" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S2253654X21001402" "doi" => "10.1016/j.remn.2021.07.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253654X21001402?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253808921001269?idApp=UINPBA00004N" "url" => "/22538089/0000004000000005/v1_202108210518/S2253808921001269/v1_202108210518/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2253808920301142" "issn" => "22538089" "doi" => "10.1016/j.remnie.2020.09.010" "estado" => "S300" "fechaPublicacion" => "2021-09-01" "aid" => "1201" "copyright" => "Sociedad Española de Medicina Nuclear e Imagen Molecular" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Esp Med Nucl Imagen Mol. 2021;40:287-92" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Tumor markers and <span class="elsevierStyleSup">18</span>F-FDG PET/CT after orchiectomy in seminoma: Is there any correlation?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "287" "paginaFinal" => "292" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Marcadores tumorales y <span class="elsevierStyleSup">18</span>F-FDG PET/CT después de orquiectomía en seminoma: ¿hay alguna correlación?" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2351 "Ancho" => 2500 "Tamanyo" => 238597 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">MIP (a), axial CT (b), axial PET (c) and axial fused PET/CT (d) images of a <span class="elsevierStyleSup">18</span>F-FDG PET/CT scan demonstrating a metastatic lesion on the posterior arch of the 8th right rib in a patient with positive hCG and negative AFP.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Francesco Dondi, Domenico Albano, Francesco Bertagna, Raffaele Giubbini" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Francesco" "apellidos" => "Dondi" ] 1 => array:2 [ "nombre" => "Domenico" "apellidos" => "Albano" ] 2 => array:2 [ "nombre" => "Francesco" "apellidos" => "Bertagna" ] 3 => array:2 [ "nombre" => "Raffaele" "apellidos" => "Giubbini" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S2253654X20301281" "doi" => "10.1016/j.remn.2020.06.019" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253654X20301281?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253808920301142?idApp=UINPBA00004N" "url" => "/22538089/0000004000000005/v1_202108210518/S2253808920301142/v1_202108210518/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Radiation exposure of the operators in the preparation and administration of yttrium-90 microspheres in the treatment of malignant hepatic lesions: What is the risk?" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "293" "paginaFinal" => "298" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Teresa Scotognella, Andrea Morasca, Luca Zagaria, Amedeo Capostosti, Roberto Iezzi, Luca Indovina, Alessandro Giordano, Germano Perotti" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Teresa" "apellidos" => "Scotognella" ] 1 => array:2 [ "nombre" => "Andrea" "apellidos" => "Morasca" ] 2 => array:2 [ "nombre" => "Luca" "apellidos" => "Zagaria" ] 3 => array:2 [ "nombre" => "Amedeo" "apellidos" => "Capostosti" ] 4 => array:2 [ "nombre" => "Roberto" "apellidos" => "Iezzi" ] 5 => array:2 [ "nombre" => "Luca" "apellidos" => "Indovina" ] 6 => array:2 [ "nombre" => "Alessandro" "apellidos" => "Giordano" ] 7 => array:2 [ "nombre" => "Germano" "apellidos" => "Perotti" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Fondazione Policlinico, Universitario Agostino Gemelli IRCSS, Italy" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Exposición a la radiación de los operadores en la preparación y administración de microesferas de itrio-90 en el tratamiento de lesiones hepáticas malignas: ¿cuál es el riesgo?" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1306 "Ancho" => 1750 "Tamanyo" => 226748 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Preparation of single dose of Sir-Sphere®.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Liver radioembolization (RE), also known as trans-arterial radioembolization (TARE) or selective internal radiation therapy (SIRT), is an emerging and promising treatment for the therapy of liver primary and secondary tumours, based on intra-arterial infusion of micro-sized embolic particles, loaded with <span class="elsevierStyleSup">90</span>Y, directly into the tumour. The rationale of this treatment is related to the possibility to obtain a selective embolic effect and, at the same time, to deliver a high radiation dose to the tumour, sparing the healthy parenchyma.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Main advantages are represented by the possibility to release high doses of radiation to small target volumes, the ability to treat the whole liver including the microscopic diseases, and the relatively low toxicity profile. However, some debated issues are related to the risk to release activity to lung, normal liver or abdominal organs, as well as radioprotection of operators.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In detail, the whole procedure is complex, involving different healthcare specialists with different areas of expertise: nuclear medicine physicians for infusion phase, interventional radiologists for angiographic phase, medical physicists for patient dosimetry phase, technicians to evaluate radioprotection measures, and radiopharmacists for the fractionation phase. In every step of therapy, the health care personnel manipulate high activities of <span class="elsevierStyleSup">90</span>Y with the risk to be exposed to high radiation dose. The radiation protection measures to be applied involve the use of low atomic number material, such as a polymethylmethacrylate (PMMA), both for preparation and infusion of microspheres. Furthermore, during and after the infusion, radiometric evaluation to the personnel and to the infusion area need to be considered.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Based on this background, considering the emerging role and increasing diffusion of radioembolization in the management of oncological patients, the aim of our study was to estimate the radiological risk for all nuclear medicine operators involved in the RE procedures.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Microspheres loaded with <span class="elsevierStyleSup">90</span>Y: properties and physical characteristics</span><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">90</span>Y is a pure β-emitting radioisotope of an average energy of 0.94 MeV with a maximum radiation range of 11 mm in the tissue and physical half-life of 64.1 h.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Following treatment with <span class="elsevierStyleSup">90</span>Y microspheres, the patient becomes a source of ionizing radiation that could potentially affect other people via Bremsstrahlung emission, as a result of <span class="elsevierStyleSup">90</span>Y β-particles interacting with the surrounding body tissues in vivo. The production of in vivo Bremsstrahlung of <span class="elsevierStyleSup">90</span>Y microspheres is sufficient for external detection and imaging. Therefore, the resulting external radiation hazard to interventional suite personnel has to be evaluated and minimized immediately after RE.</p><p id="par0025" class="elsevierStylePara elsevierViewall">At present, there are two types of <span class="elsevierStyleSup">90</span>Y microspheres commercially available: SIR-Spheres® (Sirtex Medical Limited, NSW, Australia) and Therasphere™ (BTG, London, UK). SIR-Spheres® (SIR) consist of biocompatible microspheres coated with a partially cross-linked cation exchange polystyrene resin; <span class="elsevierStyleSup">90</span>Y is incorporated into the resin matrix through ion exchange of sodium for yttrium and immobilized to the microspheres following its precipitation as a phosphate salt.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The average diameter of microspheres is 32.5 μm (range between 20 and 60 μm). Each vial contains 3 GBq of yttrium 90 (at the time of calibration) in a total of 5 mL water for injection.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The manufacturing process of Therasphere™ (TH) involves mixing <span class="elsevierStyleSup">89</span>Y with ultrapure aluminium oxide and silicone dioxide, which is then melted in a furnace at 1500 °C. After cooling, the <span class="elsevierStyleSup">89</span>Y embedded glass is crushed and passed through a flame sprayer, to obtain the sphere shape. Finally, neutron bombardment of the spheres converts the embedded <span class="elsevierStyleSup">89</span>Y to <span class="elsevierStyleSup">90</span>Y.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Y-microspheres preparation</span><p id="par0035" class="elsevierStylePara elsevierViewall">The preparation of SIR dose was carried out according to manufacturer instructions (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The procedure involves the use of accessories supplied by the same manufacturer.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> No preparation is needed for TH. The infusion of both <span class="elsevierStyleSup">90</span>Y-microspheres takes place with the accessories supplied by manufacturer, and performed according to the manufacturer instructions (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The involved operator, the radioprotection devices used and the instrumentations for radiation measurements are reported in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Dosimetry</span><p id="par0045" class="elsevierStylePara elsevierViewall">The radiometric monitoring for the radiological risk assessment to the operators concerned four phases of the procedure: a) SIR-Sphere® preparation; b) I.V. infusion of SIR and TH; c) monitoring possible surface contamination and d) monitoring the air dose rate around the patient during puncture site pressing for haemostasis.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The selected dose descriptors were Hp<span class="elsevierStyleInf">0.07</span> for the dosimetry at the fingers (a–b), the specific surface activity for the verification of the contamination (c) and the air dose rate for the extraction phase of the catheter (d).</p><p id="par0055" class="elsevierStylePara elsevierViewall">The dosimeters for fingers were of the Termoluminescence (TLD) type with thin detector for extremities, calibrated for x, gamma and beta radiation (a–b).</p><p id="par0060" class="elsevierStylePara elsevierViewall">The evaluation of the surface contamination was carried out with a proportional counter mod. LB 124 Berthold® (c).</p><p id="par0065" class="elsevierStylePara elsevierViewall">The air dose rate was measured with a detector of the proportional counter type mod FH40 G Thermo® (d).</p><p id="par0070" class="elsevierStylePara elsevierViewall">The TLD dosimeters were positioned in pair for each hand, in correspondence of the forefinger and thumb fingertips, below the sterile gloves, for a total of four dosimeters for each fractionation and infusion (a–b) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Finger exposure was monitored during the preparation of single dose and during the infusion procedure, including the preparation of the infusion set, injection of dose and collection of contaminated materials. The contamination measures involved the patient bed, the floor of the angiographic room and all the needed tools (c).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The dose measurement around the patient during the catheter extraction was performed at a distance of 0.5 m in the direction of the radiologist (d).</p><p id="par0080" class="elsevierStylePara elsevierViewall">We collected all data on appropriate modules, designed for this study (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">In this study, we did not evaluate the dose exposure related to diagnostic angiography.</p><p id="par0090" class="elsevierStylePara elsevierViewall">The procedures were performed by two senior operators and three young operators. We defined as “senior” operator who had performed at least 10 fractionation and 20 infusion procedures per year, while as “young” operator who did not performed any procedure. All operators were right-handed.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Statistical analysis</span><p id="par0095" class="elsevierStylePara elsevierViewall">For statistical analysis, the Mann-Whitney test for unpaired data was used. <span class="elsevierStyleItalic">p</span> values <0.05 was considered statistically significant.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="par0100" class="elsevierStylePara elsevierViewall">We selected, by care routine, 17 consecutive patients from September 2017 to March 2018, thirteen males and four females, with a mean ages of 62 years. Thirteen patients were affected by hepatocellular carcinoma, one patient by cholangiocarcinoma and three patients by metastatic colon-rectal carcinoma. All patients signed the informed consent to treatment.</p><p id="par0105" class="elsevierStylePara elsevierViewall">We performed 27 procedures for 17 patients: 10 preparations of single dose with the SIR and 17 infusions to the patient (10 with SIR plus 7 with TH). No technical problems were reported during the preparation and infusion of <span class="elsevierStyleSup">90</span>Y microspheres.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The mean fractionation phase time was 11 min 23 s (range 5 min 2 s - 17 min 00 s). The mean infusion phase time was 7 min 42 s for SIR (range 3 min 30 s - 13 min 07 s) and 11 min 07 s for TH (range 6 min 15 s -13 min 58 s.), respectively.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The fractionation phase (phase a) was performed only for SIR: the average fractionated activity was 3.34 GBq (range 2.7–4.0) and the average value of Hp<span class="elsevierStyleInf">0.07</span> was 0.50 mSv (range 0.05–2.20), respectively.</p><p id="par0120" class="elsevierStylePara elsevierViewall">No significant differences were found between the right <span class="elsevierStyleItalic">versus</span> the left hand (<span class="elsevierStyleItalic">p = 0.36</span>): 0.5 mSv for left hand (range 0.05–1.45), 0.50 mSv for right hand (range 0.05–2.20).</p><p id="par0125" class="elsevierStylePara elsevierViewall">Only one out of ten procedures of fractionation reported high values of Hp<span class="elsevierStyleInf">0.07</span>: right hand value of Hp<span class="elsevierStyleInf">0.07</span> was 2.20 mSv and left hand value of Hp<span class="elsevierStyleInf">0.07</span> was 1.45 mSv. The highest skin dose on fingertips measured for ten preparation was 0.15 mSv/GBq.</p><p id="par0130" class="elsevierStylePara elsevierViewall">During the infusion phase (phase b), the average SIR activity was 1.51 GBq (range 1.2–2.0) and the average TH activity was 2.10 GBq (range 1.36–3.0), respectively.</p><p id="par0135" class="elsevierStylePara elsevierViewall">For the infusion phase, the average value of Hp<span class="elsevierStyleInf">0.07</span> was 0.10 mSv (range 0.05−0.25). Particularly, the mean value of Hp<span class="elsevierStyleInf">0.07</span> for SIR was 0.09 mSv (range 0.07 – 0.11) and for TH 0.1 mSv (range 0.07 – 0.15), respectively. The difference between the mean values was no statistically significant (<span class="elsevierStyleItalic">p</span> = 0.7).</p><p id="par0140" class="elsevierStylePara elsevierViewall">Regarding the infusion phase, average values of Hp<span class="elsevierStyleInf">0.07</span> were 0.10 mSv for left hand (range 0.05−0.25) and 0.10 mSv, for right hand (range 0.05−0.25). The difference between the mean values was no statistically significant (<span class="elsevierStyleItalic">p</span> = 0.62). Particularly, the mean value of Hp<span class="elsevierStyleInf">0.07</span> was 0.08 mSv for SIR, (left hand 0.09 mSv and right hand 0.07 mSv), and 0.09 mSv (left hand 0.07 mSv and right hand 0.11 mSv) for TH, respectively.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The Hp<span class="elsevierStyleInf">0.07</span> value was calculated in senior and young operators: for senior operators, it was 0.08 mSv (range 0.05−0.15) and for young operators 0.09 mSv (range 0.05−0.25), respectively (<span class="elsevierStyleItalic">p = 0.70</span>).</p><p id="par0150" class="elsevierStylePara elsevierViewall">The highest skin dose on fingertips measured for the 17 infusions were 38 μSv/GBq and 47 μSv/GBq, for senior and young operators, respectively.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Regarding surface contamination (phase c), no contaminations were found in all 27 procedures.</p><p id="par0160" class="elsevierStylePara elsevierViewall">During the extraction of the catheter and puncture site pressing for haemostasis (phase d), we measured the air dose, considering an estimated time spent of 15 min per procedure: the average value was 0.5 µSv on body.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">The widespread use of <span class="elsevierStyleSup">90</span>Y microspheres for treatment of malignant hepatic lesions has focused the attention to the radiological risk to the involved personnel, considering the “as low as reasonably achievable” principle (ALARA). At present, two medical devices are approved for RE: resin microspheres (SIR) and glass microspheres (TH), loaded with <span class="elsevierStyleSup">90</span>Y. The glass microspheres have the advantage that the infusion must be performed with the shielded vial at a specific time, based on the calculated activity for each patient. It can decrease the radiation exposure to the operator, as compared to SIR, because the preparation phases are not required. Moreover, according to EANM Guidelines, glass microspheres can be used in patients with portal vein thrombosis and the relative absence of embolic effects does not reduce the oxygenation of tumour tissue, so improving the response to irradiation.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,6</span></a> The resin microspheres have the advantage that the activity can be fractionated for every single patient choosing the ideal administered dose and giving a major flexibility in timing of infusion. In fact, the administration phase is continuously monitored and both the position of the catheter and the rate of infusion can be changed by operator. The disadvantage is that the preparation of the dose implicates a greater radiation exposure to the operator, and the moderate embolic effect could produce hypoxia, reducing the effect of radiation.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Regarding to adverse effects, Kallini et al.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> reported in a recent review more adverse events with resin microspheres, like gastric ulcers, cholecystitis, hepatic failure and hepatobiliary complications. On the contrary, ascites and high grade nausea has been reported more frequently after glass microspheres treatment.</p><p id="par0175" class="elsevierStylePara elsevierViewall">The results of our study are encouraging: we measured very low fingertips doses, with a mean value of 0.50 mSv for fractionation phase and 0.10 mSv for infusion phase. Only one fractionation procedure showed a higher value: 2.20 and 1.45 mSv in the right and left hand, respectively. This result occurred because this procedure was repeated three times, due to an insufficient activity to be collected. We did not find significant difference in the exposure of left and right hand, both in young and senior operators, probably related to the absence of technical problems during fractionation phase and to the same contact time between both hands and microspheres during infusion phase.</p><p id="par0180" class="elsevierStylePara elsevierViewall">To our knowledge, there is only one paper in literature that analyses radiation exposure of personnel involved in RE<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>: Laffont et al. reported an exposure for fractionation of resin microsphere of 295 μSv/GBq. Our results are similar, with a mean value of 150 μSv/GBq. As reported by Laffont et al., these values are due to manual resuspension of the microspheres and the difficulty of withdrawing the prescribed activity: in some cases, it is necessary to repeat the operation two or three time. For infusion procedures, Laffont et al. reported a mean value of 17.9 μSv/GBq for young operator and 13.9 for senior: our results are higher, with 47 μSv/GBq and 38 μSv/GBq for young and senior operator, respectively. This difference is probably related to the distance between the operator and the microspheres: our operators stood near the box during the infusion procedure, Laffont et al. reported a different position, with the seated operators as far away possible from the box, with ad additional mobile acrylic screen between the operator and the box.</p><p id="par0185" class="elsevierStylePara elsevierViewall">Our finger dose values are lower than those reported in other high-risk procedures, such as treatment of neuroendocrine tumour with <span class="elsevierStyleSup">90</span>Y-DOTATOC and in the preparation of <span class="elsevierStyleSup">90</span>Y-ibritumomab tiuxetan (<span class="elsevierStyleSup">90</span>Y-Zevalin®) for treatment of non-Hodgkin’s lymphoma.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Cremonesi et al. reported a mean exposition of 0.533 mSv/GBq for manual fractionation of <span class="elsevierStyleSup">90</span>Y-DOTATOC and a mean value of 1.933 mSv/GBq for manipulation of <span class="elsevierStyleSup">90</span>Y-ibritumomab tiuxetan.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Regarding fractionation procedure, our mean value is 0.397 mSv/GBq, lower then Cremonesi et al. values. The difference is probably due to several procedures of manipulation of the vial containing radiopharmaceuticals. For infusion phase, Cremonesi et al. reported a locoregional injection with a mean value of 0.5 mSv, that compares well with our mean value of 0.1 mSv for the injection into hepatic artery.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The exposition of interventional radiologist, during the phase of catheter extraction and femoral compression, which are the most critical phases in term of body absorbed dose, is also negligible: we measured an air dose rate of 0.50 μSv on body, for an estimated mean time of 15 min. Law et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> reported similar values for radiologist, with a body dose of 0.71 μSv, for a mean time of 20 min.</p><p id="par0195" class="elsevierStylePara elsevierViewall">Our data are also comparable to Kim et al. results.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Kim et al. designed a study to estimate the possible external dose to operator from the patient after treatment of SIR and to evaluate the measured total effective dose equivalent (TEDE) at different time and distance to the patients. The obtained values of measured TEDE at 1 m from patient were in the range of 0.9–10 μSv, well comparing to our data.</p><p id="par0200" class="elsevierStylePara elsevierViewall">Projecting the doses for all the procedures foreseen for a year in our Institution (about 55), even considering them all performed by a single operator, the exposure to the fingers is 25 mSv/year, far from the annual limit required by national law DLgs 187/00 (500 mSv/year). We also compared these results with the finger dose to our nuclear medicine personnel in routine diagnostic procedures with single photon emitting radiation, for which the mean dose to the extremities is 12 mSv/year.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusion</span><p id="par0205" class="elsevierStylePara elsevierViewall">The handling of <span class="elsevierStyleSup">90</span>Y microspheres during the radioembolization procedure can be carried out under safe conditions, also for the operators without long experience. The fingers exposurein SIR and TH infusion phase is acceptable and meets the regulatory limits, without significant difference between glass and resin microspheres.</p><p id="par0210" class="elsevierStylePara elsevierViewall">However, further studies are required to investigate the radiological risk in a large number of radioembolization procedures.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Declaration</span><p id="par0215" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0220" class="elsevierStylePara elsevierViewall">Ethical Approval and Consent to participate: all the operators gave the consent to the treatment of personal data.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0225" class="elsevierStylePara elsevierViewall">Consent for publication: all authors gave the consent for publication</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0230" class="elsevierStylePara elsevierViewall">Conflict of interest: the authors declare no conflict of interest</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0235" class="elsevierStylePara elsevierViewall">Competing Interests: this research received no external funding</p></li></ul></p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1562252" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1408890" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1562251" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1408889" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Microspheres loaded with Y: properties and physical characteristics" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Y-microspheres preparation" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Dosimetry" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Declaration" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-03-24" "fechaAceptado" => "2020-05-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1408890" "palabras" => array:6 [ 0 => "Yttrium 90" 1 => "Microspheres" 2 => "Trans arterial radioembolization (TARE)" 3 => "Selective internal radiation therapy (SIRT)" 4 => "Radioprotection" 5 => "Radiological risk" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1408889" "palabras" => array:6 [ 0 => "Itrio 90" 1 => "Microesferas" 2 => "Radioembolización trans arterial (TARA)" 3 => "Radioterapia interna selectiva (RIS)" 4 => "Radioprotección" 5 => "Riesgo radiológico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Liver radioembolization is an emerging treatment against liver primary and secondary tumours. The whole procedure of radioembolization involves different health care specialists with different expertise. During the fractionation and infusion phases, the personnel manipulates high activities of <span class="elsevierStyleSup">90</span>Y. In our centre, the number of radioembolization treatments per year is increasing; the aim of this study is to monitor the dose to the operators and to estimate the radiological risk for the operators involved in the RE. At present, two medical devices are approved: Sir-Sphere® and Therasphere™, both loaded with <span class="elsevierStyleSup">90</span>Y. The dosimeters used were TLDs placed over the fingertips, for a total of 4 dosimeters for each phase; the selected dose descriptor was Hp<span class="elsevierStyleInf">0.07</span>. The study concerned 17 patients affected by malignant hepatic lesions, treated from September 2017 to March 2018. We performed 27 procedures: 10 fractionations (with Sir-Sphere®) and 17 infusions to the patients (10 with Sir-Spheres®, 7 with Theraspheres™). For fractionation phase, the average activity of each preparation was 3.34 GBq, the average value of Hp<span class="elsevierStyleInf">0.07</span> was 0.50mSv. For infusion phase, the average activity was 1.51 GBq for Sir-Sphere® and 2.10 GBq for Theraspheres™, the average value of Hp<span class="elsevierStyleInf">0.07</span> was 0.10mSv. No significant differences were found between senior (Hp<span class="elsevierStyleInf">0.07</span> = 0.08mSv) and young operators (Hp<span class="elsevierStyleInf">0.07</span> = 0.09mSv), respectively. Similarly, no significant differences were found between the right and left hand, with the same average value of Hp<span class="elsevierStyleInf">0.07</span> (0.01mSv). In conclusion, the results are encouraging, since fingertips reported doses very low. The handling of <span class="elsevierStyleSup">90</span>Y microspheres and the radioembolization procedure can be carried out under safe conditions.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La radioembolización del hígado es un tratamiento emergente contra los tumores primarios y secundarios del hígado. En todo el procedimiento de radioembolización intervienen diferentes especialistas de la atención de la salud con diferentes conocimientos especializados. Durante las fases de fraccionamiento e infusión, el personal manipula actividades de alto nivel de 90Y. En nuestro centro, el número de tratamientos de radioembolización por año está aumentando; el objetivo de este estudio es controlar la dosis a los operarios y estimar el riesgo radiológico para los operarios implicados en la ER. En la actualidad, hay dos dispositivos médicos aprobados: Sir-Sphere® y Therasphere™, ambos cargados con 90Y. Los dosímetros utilizados fueron TLDs colocados en la punta de los dedos, para un total de 4 dosímetros para cada fase; el descriptor de dosis seleccionado fue Hp0.07. El estudio abarcó 17 pacientes afectados por lesiones hepáticas malignas, tratados desde septiembre de 2017 hasta marzo de 2018. Se realizaron 27 procedimientos: 10 fraccionamientos (con Sir-Sphere®) y 17 infusiones a los pacientes (10 con Sir-Spheres®, 7 con Theraspheres™). Para la fase de fraccionamiento, la actividad media de cada preparación fue de 334 GBq, el valor medio de Hp0,07 fue de 0,50mSv. Para la fase de infusión, la actividad media fue de 151 GBq para Sir-Sphere® y 210 GBq para Theraspheres™, el valor medio de Hp0,07 fue de 0,10mSv. No se encontraron diferencias significativas entre los operadores mayores (Hp0.07 = 0.08mSv) y los jóvenes (Hp0.07 = 0.09mSv), respectivamente. Del mismo modo, no se encontraron diferencias significativas entre la mano derecha y la izquierda, con el mismo valor promedio de Hp0.07 (0.01mSv). En conclusión, los resultados son alentadores, ya que las yemas de los dedos informaron de dosis muy bajas. El manejo de las microesferas de 90Y y el procedimiento de radioembolización pueden llevarse a cabo en condiciones de seguridad.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Scotognella T., Morasca A., Zagaria L., Capostosti A., Iezzi R., Indovina L., et al. Exposición a la radiación de los operadores en la preparación y administración de microesferas de itrio-90 en el tratamiento de lesiones hepáticas malignas: ¿cuál es el riesgo?. Rev Esp Med Nucl Imagen Mol. 2021;40:293–298.</p>" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1306 "Ancho" => 1750 "Tamanyo" => 226748 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Preparation of single dose of Sir-Sphere®.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1811 "Ancho" => 1750 "Tamanyo" => 343085 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Preparation of box and microspheres infusion of Sir-Sphere® (a) and Therasphere™ (b).</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 991 "Ancho" => 1300 "Tamanyo" => 116553 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Fingertip monitoring with TLD detectors.</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1165 "Ancho" => 3167 "Tamanyo" => 306328 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Data collection forms.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Procedures \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Operators involved \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Devices/instruments \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Preparation of single dose (for Sir-Spheres®) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Nuclear Medicine Physician- Radiopharmacist- Technician \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Hot cell (NMC 1/30 + 10−20 VF)- Latex gloves- long tongs (20 cm length)- PMMA shield for syringe (2 cm thick)- PMMA shield for vial containing the single dose (2 cm thick)- TLD ring dosimeters \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infusion of dose to the patient (Sir-Spheres® and Theraspheres™) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Nuclear Medicine Physician- Interventional Radiologist- Technician \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Latex gloves- infusion system- PMMA shield for vial containing the single dose (2 cm thick)- PMMA box (2 cm thick) containing the shield vial - TLD ring dosimeters \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patient locoregional, Infusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Interventional Radiologist- Technician \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Geiger Muller probe (Thermo FH40 G)- Proportional counter (Berthold LB124) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Extraction of catheter and femoral compression \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Interventional Radiologist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">- Geiger Muller probe (Thermo FH40 G) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2677045.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Devices and instruments use for radiation protection operator <span class="elsevierStyleItalic">(PMMA = polymethylmethacrylate, TLD = thermoluminescent dosimeter)</span>.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The ten commandments of hepatic radioembolization: expert discussion and report from Mediterranean Interventional Oncology (MIOLive) congress 2017" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.L. 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