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11C-choline PET/CT and multiparametric MRI in patients with biochemical relapse of prostate cancer
11C-colina PET/TAC y RM multiparamétrica en la recidiva bioquímica del cáncer de próstata
J.R. Garciaa,
Corresponding author
jrgarcia@cetir.es

Corresponding author.
, N. Romerab, M. Cozara, M. Solera, M. Moragasa, M. Escobarb
a Unidad PET/TC, CETIR, Spain
b Servicio de Radiología, Centro Médico Teknon, Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Clinical problem with casuistry</span><p id="par0005" class="elsevierStylePara elsevierViewall">Biochemical recurrence after prostatectomy is defined as the elevation of PSA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> The definition of biochemical recurrence after radiotherapy is more controversial&#44; but an increase of 0&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml in 6&#8211;12 months is accepted&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> It is important if the recurrence is local or there exists lymph node involvement or metastatic bone involvement or a combination between them&#44; since it determines patient management&#44; being able to consider radical therapy for local recurrence&#44; but a systemic treatment&#44; combined or not with systemic treatment is necessary for metastatic disease&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Prostate biopsy is the traditional method for detecting local recurrence&#59; however&#44; it is invasive&#44; costly&#44; and it has a relatively low but not negligible complication rate &#40;such as infection&#41;&#46; Moreover&#44; the negative biopsy does not exclude local recurrence due to potential sampling error&#44; so repeat biopsy is needed&#46; Therefore&#44; the biopsy is not recommended by the EAU in patients with PSA<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In this casuistry&#44; we compared the diagnostic usefulness of PET&#47;CT with <span class="elsevierStyleSup">11</span>C-choline and multiparametric MRI in the detection of local recurrence&#44; lymph node involvement&#44; intrapelvic involvement in patients with biochemical recurrence of prostate cancer&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">We included 21 patients with a history of prostate cancer&#44; initially treated with surgery &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41; or radiotherapy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41; who had increased PSA &#40;postsurgery 0&#46;3&#8211;3&#46;6<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; postradiotherapy 2&#46;4&#8211;8&#46;8<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46; All patients underwent&#58; full body &#8216;two phase&#8217; PET&#47;CT study and multiparametric prostate MRI&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSup">11</span>C-choline has been synthesized in the cyclotron located in the same system&#46; The tracer was administered with the intracameral patient &#40;296<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29<span class="elsevierStyleHsp" style=""></span>MBq&#41; initiating the acquisition immediately&#46; After performing CT of attenuation correction&#44; 2 consecutive full body PET emission acquisition &#40;9 steps&#47;2<span class="elsevierStyleHsp" style=""></span>min&#41; were carried out&#44; without patient mobilization&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The multiparametric prostate MRI includes performing anatomical sequences&#44; diffusion study&#44; and dynamic study after administration of intravenous paramagnetic contrast&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The interpretation of PET&#47;CT with <span class="elsevierStyleSup">11</span>C-choline was performed by 2 specialists in nuclear medicine&#46; The prostate multiparametric MRI interpretation by 2 specialists in X-ray diagnosis&#46; Both were evaluated blindly from the other examination&#46; We performed analysis of the detection rate of PET&#47;CT with <span class="elsevierStyleSup">11</span>C-choline and prostate multiparametric MRI&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">From our results&#44; all patients with both scans&#44; or one of them positive&#44; underwent directed diagnostic study and&#47;or salvage treatment&#44; performing clinical&#44; analytical and imaging follow-up&#44; between 12 and 18 months&#44; revealing increased size or&#44; alternatively&#44; reduction or resolution of the lesion&#44; associated with the reduction or normalization of PSA after therapy&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The patients with the 2 negative tests have reached the diagnosis of true negative&#44; including the histological findings&#44; post-biopsy&#44; or the negative follow-up for at least 12&#8211;18 months&#44; by means of diagnostic tests&#44; without progression of the PSA level&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In 15 patients &#40;71&#46;4&#37;&#41; both examinations were concordant&#44; 4 negative&#44; and 11 positive&#58; 7 local recurrences &#40;5 postradiotherapy&#44; 2 postprostatectomy&#41;&#44; 3 unique pelvic adenopathies &#40;2 infracentimeter&#44; 3 postprostatectomy&#41;&#44; 1 local recurrente&#44; and 1 single bone metastasis &#40;1 postradiotherapy&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In 6 patients &#40;28&#46;6&#37;&#41; both examinations were discordant&#58; 3 local recurrences identified in MRI without significance in PET &#40;3 postprostatectomy&#41;&#44; 1 local recurrence identified in PET without significance in MRI &#40;postradiotherapy&#41; and 2 bone metastases identified in PET outside the field of MRI&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Commentary</span><p id="par0060" class="elsevierStylePara elsevierViewall">Choline uptake is due to deregulation of choline in the tumor cells&#46; Colin-kinase is an enzyme which is overexpressed in tumor cells&#46; Overexpression of colin-kinase is independent of Ki67 in prostate tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The MRI diffusion study&#44; by means of modified T2-weighted sequences&#44; provides information on the random motion of free water molecules&#46; The diffusion is based on the fact that the restriction of water correlates with increased cellularity&#46; The neoplastic tissue has a higher diffusion restriction&#44; with low signal on the map of diffusion coefficient &#40;ADC&#41;&#46; In the dynamic study&#44; after administration of intravenous contrast &#40;gadolinium&#41;&#44; the dynamics of contrast uptake and perfusion allows for the study of microvascular tissue&#44; and indirectly of angiogenesis&#46; 3 types of uptake curve have been described&#58; type I progressive&#59; type II plateau&#59; and type III washing&#46; The last 2 are associated with a neoplastic process&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">This different biology means that there is no correlation between both techniques&#44; as reflected in the first comparative studies&#46; Thus&#44; a superiority of multiparameter MRI over PET&#47;CT with <span class="elsevierStyleSup">18</span>F-choline has been described in detecting local recurrence in patients with small lesions and low elevation of PSA &#40;5&#8211;7<span class="elsevierStyleHsp" style=""></span>mm&#59; PSA 0&#46;8&#8211;1&#46;4<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; but with similar sensitivity in &#62;10<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Our results are consistent with the findings described&#44; and the 3 local recurrences identified postprostatectomy by means of multiparametric MRI have infracentimeter character &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Therefore&#44; the spatial resolution of PET systems&#44; around 7<span class="elsevierStyleHsp" style=""></span>mm&#44; limits the sensitivity of the examination in detection of local recurrence&#46; However&#44; local recurrence identified by means of PET&#47;CT study with <span class="elsevierStyleSup">11</span>C-choline&#44; without translation in MRI&#44; was after radiotherapy &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; probably related to signal changes that occur after this treatment in the prostate gland&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Detection of lymph node involvement is crucial in restaging of prostate cancer&#46; The low negative predictive value of the analysis due to lesions of choline PET is related to the limitation of the technique in the detection of microscopic lymph node infiltration&#46; However&#44; the scan shows a high positive predictive value&#44; which facilitates performing appropriate treatments&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">In our cases&#44; both scans showed the same detection rate&#44; even in the detection of lymph node infracentimeter infiltration &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Luboldt et al&#46; performed a comparison between MRI and PET&#47;CT with <span class="elsevierStyleSup">11</span>C-choline in the detection of bone metastases of prostate cancer&#44; describing similar results between both techniques&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> Our results are consistent with these findings &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#44; although it should be noted that PET&#47;CT as whole-body scanning has allowed for the identification of metastatic bone lesions outside the field of MRI&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Therefore&#44; this casuistry shows that PET&#47;CT with <span class="elsevierStyleSup">11</span>C-choline and multiparametric MRI have a complementary role for the detection of local recurrence of prostate cancer&#44; with similar sensitivity for the detection of lymph node infiltration&#46; PET&#47;CT with <span class="elsevierStyleSup">11</span>C-choline&#44; as whole-body technique&#44; allows for bone staging&#46; Therefore&#44; its combination is necessary for a better combination of compression in restaging of patients with prostate cancer recurrence&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">For this reason&#44; we believe that PET&#47;MRI integrated teams&#44; newly introduced&#44; can play an important role in these patients&#44; by obtaining optimal spatial and temporal data coregistration of PET and MRI&#44; adding the benefits of both&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> additionally enabling a reduction of the radiation&#44; by avoiding performance of CT study&#44; as well as improvement in the management of patients&#44; performing both examinations in a single session&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflict of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Clinic problem and case series</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess the diagnostic usefulness of <span class="elsevierStyleSup">11</span>C-choline PET&#47;CT vs&#46; multi-parametric MRI in the prostate cancer relapse&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective study of 21 patients with prostate cancer treated initially with surgery &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#61;</span><span class="elsevierStyleHsp" style=""></span>12&#41;&#44; radiotherapy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#61;</span><span class="elsevierStyleHsp" style=""></span>9&#41;&#46; PSA levels were increased &#40;post-surgery&#58; &#46;3&#8211;3&#46;6<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; post-radiotherapy&#58; 2&#46;4&#8211;8&#46;8<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In an interval of time of 15 days all patients were underwent to&#58; whole-body-dual-modality PET-CT carried out early after <span class="elsevierStyleSup">11</span>C-choline &#40;296<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29<span class="elsevierStyleHsp" style=""></span>MBq&#41; injection&#44; and multiparametric prostate MRI with paramagnetic intravenous contrast &#40;using anatomical imaging sequences&#44; diffusion-weighted imaging and dynamic contrast-enhanced imaging&#41;&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">On the basis of our results&#44; all patients were underwent to directed diagnosis and&#47;or clinical&#44; analytic and imaging follow-up&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">In 15 patients &#40;71&#46;4&#37;&#41; both procedures showed concordant results&#58; 4 negative and 11 positive cases &#91;7 local recurrences&#44; 3 isolated pelvic lymph nodes &#40;2 infracentimetric&#41;&#44; 1 local relapse and only one M1 bone metastases&#93;&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The results were discordant in 6 patients &#40;28&#46;6&#37;&#41;&#58; 3 local relapses in MRI with no PET significance&#44; 1 local relapse in PET with no MRI significance&#46; 2 bone metastases were identified with PET &#40;out of the field-of-view of MRI&#41;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Comment</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">11</span>C-choline PET&#47;CT and multi-parametric MRI play a complementary role in the detection of local relapse in prostate cancer patients&#44; with similar sensitivity for the detection of lymph involvement&#46; Whole-body <span class="elsevierStyleSup">11</span>C-choline PET&#47;CT technique is also useful for bone staging&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Problema cl&#237;nico con casu&#237;stica</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Comparar la utilidad diagn&#243;stica de la PET&#47;TC con <span class="elsevierStyleSup">11</span>C-colina y la RM multiparam&#233;trica en la detecci&#243;n de la recidiva del c&#225;ncer de pr&#243;stata a nivel p&#233;lvico&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Hemos estudiado retrospectivamente 21 pacientes con antecedente de c&#225;ncer de pr&#243;stata&#44; tratados inicialmente con cirug&#237;a &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#61;</span><span class="elsevierStyleHsp" style=""></span>12&#41; o radioterapia &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41;&#44; que presentaban elevaci&#243;n del PSA &#40;poscirug&#237;a 0&#44;3&#8211;3&#44;6<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; posradioterapia 2&#44;4&#8211;8&#44;8<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46; A todos ellos&#44; en un periodo de tiempo inferior a 15 d&#237;as&#44; se les realiz&#243;&#58; estudio PET&#47;TC &#171;doble fase&#187; de cuerpo completo&#44; inmediatamente tras la administraci&#243;n de <span class="elsevierStyleSup">11</span>C-colina &#40;296<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29<span class="elsevierStyleHsp" style=""></span>MBq&#41; y RM prost&#225;tica multiparam&#233;trica&#44; empleando secuencias anat&#243;micas&#44; estudio de difusi&#243;n y estudio din&#225;mico tras la administraci&#243;n de contraste intravenoso paramagn&#233;tico&#46; A partir de nuestros resultados&#44; a todos ellos se les realiz&#243; estudio diagn&#243;stico dirigido y&#47;o seguimiento cl&#237;nico&#44; anal&#237;tico y de imagen&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">En 15 pacientes &#40;71&#44;4&#37;&#41; ambas exploraciones fueron concordantes&#44; 4 negativas y 11 positivas&#58; 7 recidivas locales&#44; 3 adenopat&#237;as p&#233;lvicas &#250;nicas &#40;2 infracentim&#233;tricas&#41;&#44; una recidiva local y una M1 &#243;sea &#250;nica&#46; En 6 pacientes &#40;28&#44;6&#37;&#41; ambas exploraciones fueron discordantes&#58; 3 recidivas locales identificadas en la RM y sin significaci&#243;n en la PET&#44; una recidiva local identificada en la PET sin significaci&#243;n en la RM y 2 M1 &#243;seas identificadas en la PET fuera del campo de RM&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Comentario</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La PET&#47;TC con <span class="elsevierStyleSup">11</span>C-colina y la RM multiparam&#233;trica tienen un papel complementario para la detecci&#243;n de recidiva local del c&#225;ncer de pr&#243;stata&#44; con sensibilidad similar para la detecci&#243;n de inflitraci&#243;n ganglionar&#46; La PET&#47;TC con <span class="elsevierStyleSup">11</span>C-colina&#44; como t&#233;cnica de cuerpo completo&#44; permite la estadificaci&#243;n &#243;sea&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Garcia JR&#44; Romera N&#44; Cozar M&#44; Soler M&#44; Moragas M&#44; Escobar M&#46; <span class="elsevierStyleSup">11</span>C-colina PET&#47;TAC y RM multiparam&#233;trica en la recidiva bioqu&#237;mica del c&#225;ncer de pr&#243;stata&#46; Actas Urol Esp&#46; 2015&#59;39&#58;259&#8211;263&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Patient with a history of prostate cancer treated with surgery 3 years ago having high PSA &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46; &#40;A&#41; and &#40;B&#41; Dynamic study with intravenous paramagnetic contrast&#46; Postprostatectomy changes with hyperintense nodular lesion in right posterolateral vesicoureteral anastomosis&#44; with initial rapid increased uptake curve&#44; and late plateau-washing phase&#44; highly suggestive of local recurrence&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Patient with a history of prostate cancer treated with radiotherapy 2 years ago having elevated PSA &#40;2&#46;8<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46; &#40;A&#41; and &#40;B&#41; Axial early and late PET&#47;CT imaging&#46; Deposit of <span class="elsevierStyleSup">11</span>C-choline &#40;SUVmax 2&#46;0&#41; in the middle third of the right prostate lobe showing cumulative dynamics in the late imaging &#40;SUVmax 2&#46;3&#41;&#44; metabolic behavior suggestive of local recurrence&#46;</p>"
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Patient with a history of prostate cancer treated with total prostatectomy one year ago having elevated PSA &#40;0&#46;6<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46; &#40;A&#41; and &#40;B&#41; Axial early and late PET&#47;CT imaging&#46; Single hypermetabolic adenopathy &#40;SUVmax 4&#46;3&#41; in left external iliac chain with increased uptake in the late imaging &#40;SUVmax 5&#46;6&#41; suggestive of tumor lymph node involvement&#46; &#40;C&#41; T2-weighted sequence in coronal plane with surface coil&#46; Adenopathy in left iliac external chain infracentimeter of 9<span class="elsevierStyleHsp" style=""></span>mm in diameter&#46; &#40;D&#41; and &#40;E&#41; Axial plane difussion sequence with values <span class="elsevierStyleItalic">b</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0 and <span class="elsevierStyleItalic">b</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>900 and ADC map&#46; In the sequence with high b value&#44; adenopathy has marked restricted diffusion &#40;hyperintense in <span class="elsevierStyleItalic">b</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>900&#41;&#44; showing a very low ADC value &#40;hypointense in ADC map&#41;&#46;</p>"
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