Evaluation of 99m Tc labeled PSMA SPECT/CT imaging in prostate cancer patients who have undergone biochemical relapse

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1 [Downloe free from on Thursy, Ferury 16, 2017, IP: ] Asin Journl of Anrology (2017) 19, AJA, SIMM & SJTU. All rights reserve X Prostte Cner Open Aess ORIGINAL ARTICLE Evlution of T lele PSMA SPECT/CT imging in prostte ner ptients who hve unergone iohemil relpse Heng Chun Su 1,2,*, Yo Zhu 1,2,*, Guo Wen Ling 1,2, Si Long Hu 3, Xio Ping Xu 3, Bo Di 1,2, Ding Wei Ye 1,2 Using onventionl imging molities, it is iffiult to etet reurrent lesions in prostte ner ptients who hve unergone iohemil relpse, espeilly in ptients with low prostte speifi ntigen (PSA) levels. We retrospetively reviewe the files of fifty ptients with histopthologilly onfirme prostte ner who unerwent T lele prostte speifi memrne ntigen (PSMA) single photon emission ompute tomogrphy (SPECT)/ompute tomogrphy (CT), mgneti resonne imging (MRI), n one sn within 30 y perio. PSMA SPECT/CT inite metstti lesions in 39 ptients n h higher etetion rte (78.0%) thn one sn (34.0%) or MRI (40.0%). The ignosti effiieny of PSMA SPECT/CT imging for one n lymph noe metstses (50.0% n 42.0%) ws etter thn one sn (34.0% n 0.0%) or MRI (24.0% n 20.0%). PSMA SPECT/CT provie higher etetion rte t serum PSA levels of 1 ng ml 1, 1 4 ng ml 1, 4 10 ng ml 1, n >10 ng ml 1. No orreltion ws foun etween Gleson sore, PSA level, n the trer tumor/kgroun rtio of metstti lesions. With the i of PSMA SPECT/CT imging, the therpeuti strtegy ws hnge for 31 ptients, n this my hve enhne their linil outome. In onlusion, PSMA SPECT/CT imging oul etet more metstti lesions n hieve higher etetion rte thn onventionl imging molities t ifferent serum PSA levels in prostte ner ptients who h unergone iohemil relpse. Asin Journl of Anrology (2017) 19, 1 5; oi: / X ; pulishe online: 13 Deemer 2016 Keywors: T; CT; prostte ner; PSMA; SPECT INTRODUCTION Prostte ner (PC) is the seon most ommon use of eth in evelope ountries n is the most ommon soli ner in men. 1 The therpeuti tretment of PC is priniplly influene y the presene or sene of metstses. However, the etetion of reurrent isese is urrently mjor hllenge using onventionl imging molities, espeilly t low prostte speifi ntigen (PSA) levels. Stuies employing ompute tomogrphy (CT), mgneti resonne imging (MRI), n one sn hve shown isppointing sensitivity rtes in the etetion of smll metstses, inluing lymph noe metstses. 2 A etter ignosti proeure is require to lolize reurrenes in PC ptients who hve unergone iohemil relpse. Prostte speifi memrne ntigen (PSMA) hs reently reeive inresing mounts of ttention. 3,4 PSMA is expresse in tissues suh s the kiney, proximl smll intestine, n slivry glns n is lso overexpresse in PC. 5 As suh, PSMA provies promising trget for PC speifi imging n therpy. 68 G PSMA positron emission tomogrphy (PET) imging hs een reporte to improve the etetion of metstti isese, even t low serum PSA vlues. 6,7 In this retrospetive nlysis, we ompre the use of novel single photon emission CT (SPECT) imging trer, HYNIC Glu Ure A ( T lele PSMA lign), with onventionl imging molities, suh s one sn n MRI, in the ignosis of reurrene in PC ptients who h unergone iohemil reurrene. 8 MATERIALS AND METHODS Ptients For this retrospetive nlysis, we selete fifty onseutive ptients who h unergone PSMA SPECT/CT, pelvi MRI, n one sn within 30 y perio. All ptients h reeive histopthologil ignosis of PC. In ll ses, progressive isese ws suspete following onventionl PC tretment (hormone therpy, hemotherpy, rition therpy, n/or surgery). The serum PSA level of ll ptients ws >0.20 ng ml 1 when they unerwent imging. All ptients h signe written informe onsent form llowing nonymize evlution n pulition of their t, n the Lol Ethis Committee pprove this retrospetive nlysis. Tle 1 shows the linil hrteristis of ll the ptients. Imging T lele HYNIC Glu Ure A ws injete s n intrvenous olus, n whole oy SPECT n nonontrst enhne (low ose) CT sn were performe 2 h postinjetion. Attenution orretion ws performe using the low ose nonenhne CT t. No verse effets were oserve in ny of the ptients fter trer injetion. 1 Deprtment of Urology, Fun University Shnghi Cner Center, Shnghi, Chin; 2 Deprtment of Onology, Shnghi Meil College, Fun University, Shnghi, Chin; 3 Deprtment of Nuler Meiine, Fun University Shnghi Cner Center, Shnghi, Chin. * These uthors ontriute eqully to this work. Corresponene: Dr. DW Ye (wyeli@163.om) Reeive: 22 My 2016; Revise: 06 August 2016; Aepte: 13 Otoer 2016

2 [Downloe free from on Thursy, Ferury 16, 2017, IP: ] PSMA SPECT/CT in PC ptients with iohemil relpse HC Su et l 2 Consistent results whether the lesions ientifie y PSMA SPECT/CT were metstti or not were otine y isussion of the three experiene nuler meiine experts with their experiene in imge nlysis. Any nonphysiologil fol res of inrese uptke tht were higher thn the kgroun level were interprete s suspiious of prostte ner, lymph noe metstsis, one metstsis, or soft tissue metstsis. The tumor/kgroun (T/B) rtio ws lulte from regions of interest tht were mnully rwn over the sites of inrese uptke. For kgroun orretion, region of interest ws rwn over the gluteus musle. In ses of multiple metstses, only the five lesions with the highest intensity were inlue for further nlysis. Sttistil nlysis For sttistil nlysis, eite sttistil softwre ws use (SPSS 15.0; SPSS In., Chigo, Illinois, USA). Correltions etween the Gleson sore, PSA levels, n T/B rtio were ssesse using the Spermn s rnk orreltion oeffiient. All results re expresse s the men ± stnr evition. P < 0.05 ws onsiere sttistilly signifint. RESULTS Presene of PSMA positive lesions No verse or linilly etetle phrmologil effets were oserve in ny of the ptients fter injetion of the PSMA SPECT/CT trers. PSMA SPECT/CT inite metstti lesions in 39 ptients n h higher etetion rte (78.0%); there were 46 lymph noe metstses, 95 one metstses, n six soft tissue metstses (two pulmonry n four hepti) etete (Figure 1). The mein ge ws 71 yers (interqurtile rnge: 67-75). The mein PSA vlue ws 7.61 ng ml -1 (interqurtile rnge: ). The T/B rtio ws highest in lymph noe metstses (37.42 ± 6.65). Soft tissue (26.33 ± 9.07) n one metstses (21.40 ± 4.34) h lower Tle 1: The linil hrteristis of ll the ptients T/B rtios lthough no signifint ifferene in the T/B rtio ws foun etween lymph noe, soft tissue, n one metstses (Figure 1). There were no orreltions etween the Gleson sore, PSA level, n T/B rtio of the metstti lesions. Comprison with ifferent imging molities With the help of one sn, metstti one lesions were foun in 15 ptients, suspiious one lesions in two ptients, n norml results in 33 ptients. PSMA/SPECT imging onfirme one metstses in 15 ptients. In ptients with suspiious one lesions, one ptient ws emonstrte y PSMA SPECT/CT. In ition, 23 ptients who h norml one sns were shown to hve multiple metstti one or lymph noe metstses using PSMA SPECT/CT imging. In generl, one lesions (n = 35) were oserve in 17 ptients y one sn (etetion rtio: 34.0%) (Figure 1). Using MRI sns, metstti lesions were foun in twenty ptients n norml results in thirty ptients. PSMA SPECT/CT imging onfirme metstses in ll twenty ptients n showe itionl metstti lesions in 19 ptients. In generl, metstti lesions (n = 35) were oserve in twenty ptients y MRI imging (etetion rtio: 40.0%) (Figure 1). PSMA SPECT/CT imging oul fin 95 one metstses in 25 ptients (50.0%). Bone sn oul fin 35 one metstses in 17 ptients (34.0%). MRI oul fin twenty one metstses in 12 ptients (24.0%). The ignosti effiieny on one metstses with PSMA SPECT/CT imging ws etter thn one sn n MRI (Figure 2). PSMA SPECT/CT ws more effiient t ignosing lymph noe n soft tissue metstses. Using PSMA SPECT/CT, 46 metstti lymph noe lesions were etete in 21/50 (42.0%) of ptients; MRI inite 15 metstti lesions in 10/50 (20.0%) of ptients (Figure 2). In ition, PSMA SPECT/CT imging ientifie six soft tissue metstses in 6/50 (12.0%) of ptients, ut MRI n one sn foun no soft tissue metstses (Figure 2). Cliniopthologil feture Numer of ptients (n) Gleson sore Not ville 5 Prior tretment Surgil 30 Rition 16 Hormonl therpy 42 IQR: interqurtile rnge; PSA: prostte speifi ntigen Figure 1: Comprison of ifferent imging molities for metstti lesions in PC ptients. () Prostte speifi memrne ntigen (PSMA) single photon emission ompute tomogrphy (SPECT)/ompute tomogrphy (CT) imging provie higher etetion rtio thn one sn or mgneti resonne imging (MRI). () The tumor/kgroun (T/B) rtio ws higher for lymph noe metstses thn soft tissue or one metstses. e Figure 2: The ignosti effiieny of PSMA SPECT/CT imging for ifferent metstti lesions in PC ptients. The effiieny of PSMA SPECT/CT imging in () ignosing one, () lymph noe, n () soft tissue metstses ws greter thn one sn or MRI. The ignosti effiieny on () pelvi lymph noe metstses n (e) pelvi one metstses with PSMA SPECT/CT imging ws etter thn one sn n MRI. Asin Journl of Anrology

3 [Downloe free from on Thursy, Ferury 16, 2017, IP: ] PSMA SPECT/CT in PC ptients with iohemil relpse HC Su et l 3 The etetion effiieny y MRI, one sn, n PSMA SPECT/CT imging for pelvi metstses ws lso ompre. For etetion of lymph noes metstses, using PSMA SPECT/CT, thirty metstti lymph noe lesions were etete in 18/50 (36.0%) of ptients. MRI inite 15 metstti lesions in 10/50 (20.0%) of ptients (Figure 2). For etetion of one metstses, PSMA SPECT/CT imging foun fifty one metstses in 20/50 (40.0%) of ptients. Bone sn oul fin 15 one metstses in 10/50 (20.0%) of ptients. MRI oul fin twenty one metstses in 12/50 (24.0%) of ptients (Figure 2e). The ignosti effiieny on pelvi lymph noe n one metstses with PSMA SPECT/CT imging ws etter thn one sn n MRI. In our retrospetive nlysis, we foun tht PSMA SPECT/ CT etete five lesions in 3/10 (30.0%) of ptients with 1 ng ml 1 PSA; in ptients with 1 4 ng ml 1 PSA, twenty lesions were ientifie in 8/10 (80.0%) of ptients; in ptients with 4 10 ng ml 1 PSA, twenty lesions were ientifie in 5/5 (100%) of ptients; n in ptients with >10 ng ml 1 PSA, 102 lesions were ientifie in 23/23 (100%) of ptients (Figure 3). Using the sme threshols, MRI etete one lesion in 1/10 (10.0%) of ptients with 1 ng ml 1 PSA; in ptients with 1 4 ng ml 1 PSA, nine lesions were ientifie in 5/10 (50.0%) of ptients; in ptients with 4 10 ng ml 1 PSA, three metstti lesions were foun in 2/5 (40.0%) of ptients; n in ptients with >10 ng ml 1 PSA, 22 lesions were ientifie in 12/23 (52.0%) of ptients (Figure 3). Using the sme threshols, one sn ientifie one metstti one lesion in 1/10 (10.0%) of ptients with 1 ng ml 1 PSA; in ptients with 1 4 ng ml 1 PSA, two metstti one lesions were ientifie in 2/10 (20.0%) of ptients; in ptients with 4 10 ng ml 1 PSA, three metstti one lesions were foun in 2/5 (40.0%) of ptients; n in ptients with >10 ng ml 1 PSA, 27 lesions were ientifie in 10/23 (43.5%) of ptients n two suspiious lesions were foun in 2/23 (8.7%) of ptients (Figure 3). Clinil onsequenes Following the ientifition of itionl lolize metstti lesions using PSMA SPECT/CT imging, 15 ptients ll reeive nrogen eprivtion therpy (ADT) n PSA ontrol were not stisftory. After seletive riotherpy, PSA levels of these ptients erese, initing tht the PSMA positive lesions were PC metstses (Figure 4). Following PSMA SPECT/CT imging, the Figure 3: The ignosti effiieny of PSMA SPECT/CT imging t rnge of serum PSA levels in PC ptients. PSMA SPECT/CT provie higher etetion rte t serum prostte speifi ntigen levels of () 1 ng ml 1, () 1 4 ng ml 1, () 4 10 ng ml 1, n () >10 ng ml 1. therpeuti strtegy of ten ptients ws hnge from stnr pelvi lymphenetomy to n extene pelvi lymphenetomy n the PSMA positive lesions were lso proven to e PC y histology (Figure 5). In ition, six ptients hnge the therpeuti strtegies fter PSMA SPECT/CT showing multiple one metstsis n reeive ADT or hemotherpy with oetxel (Figure 6). In summry, PSMA SPECT/CT imging provie vlule itionl eviene to support further tretment n my hve improve the therpeuti strtegy of 31 ptients (Supplementry Informtion). DISCUSSION PC is one of the most ommon ners, n unerstning the ext ignosis n the lotion of reurrene is essentil for its mngement. 9 However, it n e iffiult to onut urte stging n etet erly reurrene, espeilly t low PSA levels, using onventionl imging molities. 2 T methylene iphosphonte one sn is the primry imging proeure for ignosing one metstsis. However, one sn hs low speifiity, n mny enign one lesions n show inrese riotrer uptke, leing to flse positive results. 10 MRI is lso ommonly use for PC ignosis. However, for ptients with low PSA levels, the MRI etetion rte is low, n it n e iffiult to etet metstti lesions tht overlp musles using this molity. PSMA is trnsmemrne ell surfe protein tht is expresse in ll stges of PC. The expression of PSMA inreses with tumor ggressiveness, metstti isese, n isese reurrene. As suh, PSMA is n exellent trget for PC imging G PSMA PET/CT imging is useful in ignosing n stging prostte ner. However, PET is not lwys ville in Chin, espeilly in the remote res. Furthermore, PET is lso more expensive thn SPECT/CT imging. All these ftors inite tht PSMA se SPECT imging oul ply n importnt role in PC imging, espeilly in institutions n res where PET is not ville. Some stuies hve shown tht 111 In lele nti PSMA nnooy esigne for trgete SPECT/CT imging lso exhiits goo tumor trgeting with low uptke in nontrget tissues, llowing exellent SPECT/CT imging of PC. 12,13 In ition, T MIP 1404 n T MIP 1405 lele PSMA SPECT/CT n ientify the mjority of metstti one lesions n rpily etete soft tissue PC lesions, inluing suentimeter lymph noes metstses. 14,15 However, to te, few stuies hve investigte the effiy of SPECT/CT imging using T HYNIC Glu Ure A in the ignosis of PC ptients who hve unergone iohemil reurrene. In this retrospetive nlysis, we investigte the effiy of T HYNIC Glu Ure A SPECT/CT imging for the etetion of metstti PC lesions. We foun tht PSMA SPECT/CT ws useful for evluting metstti lesions in PC ptients. High riotrer uptke ws oserve t the sites of one, lymph noe, n soft tissue metsttes. A high T/B uptke rtio is vntgeous in the evlution of suspete lesions, n, onsistent with previous stuy, 16 we foun no orreltion etween the Gleson sore, PSA level, n the T/B rtio. Lymph noe, one, n soft tissue metstses ommonly our in PC, n these metstses re verse prognosti ftors. 17,18 Using PSMA SPECT/CT imging, we oserve high levels of riotrer uptke t the site of metstti lesions, n, regrless of the lesion size, the etetion rte ws higher thn either MRI or one sn. In ition, PSMA SPECT/CT helpe onfirm the ignosis of PC in ptients with suspiious metstti lesions n helpe improve therpeuti sheules. In this retrospetive nlysis, PSMA SPECT/ CT might ffet the linil outomes of 31 ptients in positive wy. Asin Journl of Anrology

4 [Downloe free from on Thursy, Ferury 16, 2017, IP: ] PSMA SPECT/CT in PC ptients with iohemil relpse HC Su et l 4 Figure 4: Exmple results for ptient who reeive selete rition therpy. The ptient ws 70 yer ol mle with iopsy proven prostte ner Gleson sore of 9. After ril prosttetomy (RP), PSA level inrese to 4 ng ml 1 n he eme refrtory to nrogen eprivtion therpy (ADT). PSMA SPECT/CT imging inite lymph noe metstses ner the left ili loo vessels ([] Whole-oy plnr imges; [] CT plin sn n [] fuse PSMA-SPECT/CT imges.). MRI ws unle to onfirm the metstti lymph noe. Following PSMA SPECT/CT imging, the ptient reeive selete rition therpy n his PSA level erese to 1.20 ng ml 1. e Figure 6: Exmple results for ptient who reeive hemotherpy with oetxel. The ptient ws 50 yer ol mle with iopsy proven prostte ner Gleson sore of 10 n PSA level of 110 ng ml 1. MRI showe prostte ner ompnie y enlrge pelvi lymph noes n one sn showe no metstti one lesions. The ptient ws rey to unergo slvge RP, ut the therpeuti strtegy ws hnge fter PSMA SPECT/CT imging showe multiple metstti lesions () in the pelvis, () prostte ner, () ner to the ili loo vessels n t ( n ) vertere n (e) meistinl sites. The ptient reeive hemotherpy with oetxel n his PSA level erese to 3 ng ml 1. The metstti lesions re inite y rrows. Sine whole oy MRI is time onsuming n expensive, pelvi MRI n one sn re use to ignose PC y most urologists in Chin. In this retrospetive nlysis, we foun tht the ignosti effiieny on pelvi lymph noe n one metstses with PSMA SPECT/CT imging ws etter thn one sn n MRI. In ition, PSMA SPECT/CT imging ws heper n provie more informtion lso informtion tht the regulr urologist ws more le to unerstn y himself (inste of interpreting imging of whole oy MRI), whih helpe guie linil ignosis. This retrospetive nlysis hs ertin limittions, suh s its smll ptient popultion. Another limittion is tht the one n lymph noe lesions ientifie using PSMA SPECT/CT were not pthologilly onfirme. As suh, it is possile tht there were some flse positive lesions ientifie. However, 15 ptients who were trete with seletive rition following PSMA SPECT/CT imging, susequently, showe erese PSA levels, initing tht the PSMA positive lesions were most proly PC. In ition, in ten ptients, the PSMA positive lesions were histologilly shown to e PC. Further nlyses re Asin Journl of Anrology e Figure 5: Exmple results for ptient who reeive RP n extene pelvi lymphenetomy. The ptient ws 62 yer ol mle with iopsy proven prostte ner Gleson sore of 8 n PSA level of 46 ng ml 1. PSMA SPECT/ CT inite lymph noe metstses ner the left ili loo vessels ([] Whole-oy plnr imges; [] oronl plne of CT plin sn; [] oronl plne of fuse PSMA-SPECT/CT imges; [] vertil plne of CT plin sn; [e] vertil plne of fuse PSMA-SPECT/CT imges.). Following PSMA SPECT/ CT imging, the ptient unerwent RP n extene pelvi lymphenetomy. The PSMA positive lesions ner the left ili loo vessels were proven to e prostte ner using histology. After surgery, the ptient reeive ADT n his PSA level erese to 0.10 ng ml 1. Arrows inite metstti lymph noe lesions etete using PSMA SPECT/CT. require to onfirm our finings n to verify the sensitivity n speifiity of PSMA SPECT/CT imging in the etetion of metstti lesions in PC ptients. CONCLUSIONS At rnge of serum PSA levels, PSMA SPECT/CT imging ientifie more metstti lesions n provie higher etetion rte thn onventionl imging molities. This helpe guie linil ignosis n tretment, whih inites the vlue of PSMA SPECT/CT imging in the evlution of metstsis in PC ptients who hve unergone iohemil relpse, even in ptients with low PSA levels. AUTHOR CONTRIBUTIONS HCS n YZ esigne the retrospetive nlysis, ollete, nlyze, n interprete the linil t, n wrote n revise the mnusript. GWL, SLH, n XPX helpe ollet the linil t. BD revise the mnusript. DWY supervise the projet n revise the mnusript. All uthors re n pprove the finl mnusript. COMPETING INTERESTS All uthors elre no ompeting interests. ACKNOWLEDGMENTS This work ws supporte y the Shnghi Rising Str Progrm (No. 16QA )

5 [Downloe free from on Thursy, Ferury 16, 2017, IP: ] PSMA SPECT/CT in PC ptients with iohemil relpse HC Su et l 5 n the Ntionl Nturl Siene Fountion of Chin (Grnt No , n ). All these stuy sponsors hve no roles in the stuy esign, in the olletion, nlysis, n interprettion of t. Supplementry informtion is linke to the online version of the pper on the Asin Journl of Anrology wesite. REFERENCES 1 Brwley OW. Prostte ner epiemiology in the Unite Sttes. Worl J Urol 2012; 30: Kosuri S, Akhtr NH, Smith M, Osorne JR, Tgw ST. Review of slvge therpy for iohemilly reurrent prostte ner: the role of imging n rtionle for systemi slvge trgete nti prostte speifi memrne ntigen rioimmunotherpy. Av Urol 2012; 2012: Eer M, Shäfer M, Buer Wüst U, Hull WE, Wängler C, et l. 68 G omplex lipophiliity n the trgeting property of ure se PSMA inhiitor for PET imging. Bioonjug Chem 2012; 23: Murer T, Eier M, Shwiger M, Gshwen JE. Current use of PSMA PET in prostte ner mngement. Nt Rev Urol 2016; 13: Afshr Oromieh A, Mlher A, Eer M, Eisenhut M, Linhrt HG, et l. PET imging with (G 68) gllium lelle PSMA lign for the ignosis of prostte ner: ioistriution in humns n first evlution of tumour lesions. Eur J Nul Me Mol Imging 2013; 40: Afshr Oromieh A, Herkorn U, Shlemmer HP, Fenhel M, Eer M, et l. Comprison of PET/CT n PET/MRI hyri systems using 68 G lelle PSMA lign for the ignosis of reurrent prostte ner: initil experiene. Eur J Nul Me Mol Imging 2014; 41: Bluemel C, Kres M, Polt B, Linke F, Eier M, et l. 68 G PSMA PET/CT in ptients with iohemil prostte ner reurrene n negtive 18F holine PET/CT. Clin Nul Me 2016; 41: Xu XP, Zhng JP, He SM, Luo JM, Bo X, et l. The imging stuy of smll moleulr inhiitor trgeting prostte speifi memrne ntigen. Onoriology 2015; 3: [In Chinese]. 9 Crroll PR, Prsons JK, Anriole G, Bhnson RR, Cstle EP, et l. NCCN guielines insights: prostte ner erly etetion, version J Ntl Compr Cn Netw 2016; 14: Kskl L, Demiri E, Ok M, Akyel R, Nemtyzr J, et l. Evlution of PSMA PET/CT imging using 68 G HBED CC lign in ptients with prostte ner n the vlue of erly pelvi imging. Nul Me Commun 2015; 36: Perner S, Hofer MD, Kim R, Shh RB, Li H, et l. Prostte speifi memrne ntigen expression s preitor of prostte ner progression. Hum Pthol 2007; 38: Chtli KL, Velhoven Zweistr J, Bolkestein M, Hoeen S, Koning GA, et l. A novel 111 In lele nti prostte speifi memrne ntigen nnooy for trgete SPECT/ CT imging of prostte ner. EJNMMI Res 2015; 56: Shottelius M, Wirtz M, Eier M, Murer T, Wester HJ. [111In] PSMA I&T: expning the spetrum of PSMA I n T pplitions towrs SPECT n rioguie surgery. EJNMMI Res 2015; 5: Vllhjosul S, Nikolopoulou A, Bih JW, Osorne JR, Tgw ST, et l. T lele smll moleule inhiitors of prostte speifi memrne ntigen: phrmokinetis n ioistriution stuies in helthy sujets n ptients with metstti prostte ner. J Nul Me 2014; 55: Hillier SM, Mres KP, Lu G, Merkin RD, Mrquis JC, et l. T lele smll moleule inhiitors of prostte speifi memrne ntigen for moleulr imging of prostte ner. J Nul Me 2013; 54: Dietlein M, Koe C, Kuhnert G, Stokter S, Fisher T, et l. Comprison of [ 18 F] DCFPyL n [ 68 G] GPSMA HBED CC for PSMA PET imging in ptients with relpse prostte ner. Mol Imging Biol 2015; 17: Gkis G, Boorjin SA, Brignti A, Joniu S, Krznshvili G, et l. The role of ril prosttetomy n lymph noe issetion in lymph noe positive prostte ner: systemti review of the literture. Eur Urol 2014; 66: Hek MM, Souvtzoglou M, Retz M, Nwroth R, Küler H, et l. Prospetive omprison of ompute tomogrphy, iffusion weighte mgneti resonne imging n [ 11 C] holine positron emission tomogrphy/ompute tomogrphy for preopertive lymph noe stging in prostte ner ptients. Eur J Nul Me Mol Imging 2014; 41: This is n open ess rtile istriute uner the terms of the Cretive Commons Attriution NonCommeril ShreAlike 3.0 Liense, whih llows others to remix, twek, n uil upon the work non ommerilly, s long s the uthor is reite n the new retions re liense uner the ientil terms. Asin Journl of Anrology

6 [Downloe free from on Thursy, Ferury 16, 2017, IP: ] Supplementry Informtion This se ws 67 yer ol mle ptient with iopsy proven prostte ner Gleson sore of 10. The PSA level ws 24 ng ml 1. This ptient reeive ril prosttetomy n pthologil results showe prostte ner whih h spre to seminl vesile n right pelvi lymph noes. After the surgery, this ptient reeive ADT n PSA erese to 0.01 ng ml 1. One yer lter, PSA level inrese to 1.25 ng ml 1. Bone sn n MRI showe no metstti lesions in this ptient (Supplementry Figures 1 n 2). TC lelle PSMA SPECT/CT imging showe suspiious lymph noe metstses ner the left ili loo vessels n retroperitonel lesions (Supplementry Figure 3). As result, this ptient reeive retroperitonel lymph noe issetion n extene pelvi lymphenetomy. The pthologil results were onsistent with the results of PSMA SPECT/CT, whih showe lymph noe metstses ner the left ili loo vessels n in ominl ort jent to the ifurtion. After the surgery, PSA level erese to 0.08 ng ml 1. Supplementry Figure 1: Bone sn showe no metstti lesions in this ptient.

7 [Downloe free from on Thursy, Ferury 16, 2017, IP: ] Supplementry Figure 2: MRI showe no metstti lesions in this ptient. Supplementry Figure 3: T lelle PSMA SPECT/CT imging showe suspiious lymph noe metstses ner the retroperitonel lesions ([] CT plin sn; [] fuse PSMA-SPECT/CT imges) n left ili loo vessels ([] CT plin sn; [] fuse PSMA-SPECT/CT imges).