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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 3/2018

Open Access 01-03-2018 | Review Article

Current status of theranostics in prostate cancer

Authors: Irene Virgolini, Clemens Decristoforo, Alexander Haug, Stefano Fanti, Christian Uprimny

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2018

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Abstract

The aim of this review is to report on the current status of prostate-specific membrane antigen (PSMA)-directed theranostics in prostate cancer (PC) patients. The value of 68Ga-PSMA-directed PET imaging as a diagnostic procedure for primary and recurrent PC as well as the role of evolving PSMA radioligand therapy (PRLT) in castration-resistant (CR)PC is assessed. The most eminent data from mostly retrospective studies currently available on theranostics of prostate cancer are discussed. The current knowledge on 68Ga-PSMA PET/CT implicates that primary staging with PET/CT is meaningful in patients with high-risk PC and that the combination with pelvic multi parametric (mp)MR (or PET/mpMR) reaches the highest impact on patient management. There may be a place for 68Ga-PSMA PET/CT in intermediate-risk PC patients as well, however, only a few data are available at the moment. In secondary staging for local recurrence, 68Ga-PSMA PET/mpMR is superior to PET/CT, whereas for distant recurrence, PET/CT has equivalent results and is faster and cheaper compared to PET/mpMR. 68Ga-PSMA PET/CT is superior to 18F / 11Choline PET/CT in primary staging as well as in secondary staging. In patients with biochemical relapse, PET/CT positivity is directly associated with prostate-specific antigen (PSA) increase and amounts to roughly 50% when PSA is raised to ≤0.5 ng/ml and to ≥90% above 1 ng/ml. Significant clinical results have so far been achieved with the subsequent use of radiolabeled PSMA ligands in the treatment of CRPC. Accumulated activities of 30 to 50 GBq of 177Lu-PSMA ligands seem to be clinically safe with biochemical response and PERCIST/RECIST response in around 75% of patients along with xerostomia in 5–10% of patients as the only notable side effect. On the basis of the current literature, we conclude that PSMA-directed theranostics do have a major clinical impact in diagnosis and therapy of PC patients. We recommend that 68Ga-PSMA PET/CT should be performed in primary staging together with pelvic mpMR in high-risk patients and in all patients for secondary staging, and that PSMA-directed therapy is a potent strategy in CRPC patients when other treatment options have failed. The combination of PSMA-directed therapy with existing therapy modalities (such as 223Ra-chloride or androgen deprivation therapy) has to be explored, and prospective clinical multicenter trials with theranostics are warranted.
Literature
1.
2.
Bander NH, Trabulsi EJ, Kostakoglu L, Yao D, Vallabhajosula S, Smith-Jones P, et al. Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate-specific membrane antigen. J Urol. 2003;170:1717–21.PubMedCrossRef
3.
Eder M, Schäfer M, Bauder-Wüst U, Hull WE, Wängler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23:688–97.PubMedCrossRef
4.
Afshar-Oromieh A, Haberkorn U, Eder M, Eisenhut M, Zechmann CM. [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of PC: comparison with 18F–FECH. Eur J Nucl Med Mol Imaging. 2012;39:1085–6.PubMedCrossRef
5.
Pinto JT, Suffoletto BP, Berzin TM, Qiao CH, Lin S, Tong WP, et al. Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. Clin Cancer Res. 1996;2:1445–51.PubMed
6.
Israeli RS, Powell CT, Fair WR, Heston WD. Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res. 1993;53:227–30.PubMed
7.
Perner S, Hofer MD, Kim R, Shah RB, Li H, Möller P, et al. Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum Pathol. 2007;38:696–701.PubMedCrossRef
8.
Ross JS, Sheehan CE, Fisher HA, Kaufman RP Jr, Kaur P, Gray K, et al. Correlation of primary tumour prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res. 2003;9:6357–62.PubMed
9.
Gorin MA, Rowe SP, Hooper JE, Kates M, Hammers HJ, Szabo Z, et al. PSMA-targeted 18F-DCFPyL PET/CT imaging of clear cell renal cell carcinoma: results from a rapid autopsy. Eur Urol. 2017;71:145–6.PubMedCrossRef
10.
Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. 68Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for PC imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017;44:1014–24.PubMedCrossRef
11.
12.
13.
Mohler JL, Armstrong AJ, Bahnson RR, D’Amico AV, Davis BJ, Eastham JA, et al. Prostate cancer, version 1.2016. J Natl Compr Cancer Netw. 2016;14:19–30.CrossRef
14.
Briganti A, Larcher A, Abdollah F, Capitanio U, Gallina A, Suardi N, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol. 2012;61:480–7.PubMedCrossRef
15.
Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on PC. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71:618–29.PubMedCrossRef
16.
Punnen S, Cooperberg MR, D’Amico AV, Karakiewicz PI, Moul JW, Scher HI, et al. Management of biochemical recurrence after primary treatment of prostate cancer: a systematic review of the literature. Eur Urol. 2013;64:905–15.PubMedCrossRef
17.
Ceci F, Castellucci P, Mapelli P, Incerti E, Picchio M, Fanti S. Evaluation of PC with 11C-choline PET/CT for treatment planning, response assessment, and prognosis. J Nucl Med. 2016;57(Suppl 3):49–54.CrossRef
18.
Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter 223Ra and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.PubMedCrossRef
19.
Pfannkuchen N, Meckel M, Bergmann R, Bachmann M, Bal C, Sathekge M, et al. Novel radiolabeled bisphosphonates for PET diagnosis and endoradiotherapy of bone metastases. Pharmaceuticals (Basel). 2017 May 18;10(2).
20.
Iagaru AH, Mittra E, Colletti PM, Jadvar H. Bone-targeted imaging and radionuclide therapy in PC. J Nucl Med. 2016;57(Suppl 3):19–24.CrossRef
21.
Herrmann K, Larson SM, Weber WA. Theranostic concepts: more than just a fashion trend—introduction and overview. J Nucl Med. 2017;58:1S–2S.PubMedCrossRef
22.
Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, et al. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013;40:486–95.PubMedCrossRef
23.
Benešová M, Schäfer M, Bauder-Wüst U, Afshar-Oromieh A, Kratochwil C, Mier W, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of PC. J Nucl Med. 2015;56:914–20.PubMedCrossRef
24.
Weineisen M, Schottelius M, Simecek J, Baum RP, Yildiz A, Beykan S, et al. 68Ga- and 177Lu-Labeled PSMA I&T: optimization of a PSMA-targeted theranostic concept and first proof-of-concept human studies. J Nucl Med. 2015;56:1169–76.PubMedCrossRef
25.
Robu S, Schottelius M, Eiber M, Maurer T, Gschwend J, Schwaiger M, et al. Preclinical evaluation and first patient application of 99mTc-PSMA-I&S for SPECT imaging and radioguided surgery in PC. J Nucl Med. 2017;58:235–42.PubMedCrossRef
26.
Hillier SM, Maresca KP, Lu G, Merkin RD, Marquis JC, Zimmerman CN, et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of PC. J Nucl Med. 2013;54:1369–76.PubMedCrossRef
27.
Barrett JA, Coleman RE, Goldsmith SJ, Vallabhajosula S, Petry NA, Cho S, et al. First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging PC. J Nucl Med. 2013;54:380–7.PubMedCrossRef
28.
Cho SY, Gage KL, Mease RC, Senthamizhchelvan S, Holt DP, Jeffrey-Kwanisai A, et al. Biodistribution, tumour detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with mPC. J Nucl Med. 2012;53:1883–91.PubMedPubMedCentralCrossRef
29.
Chen Y, Pullambhatla M, Foss CA, Byun Y, Nimmagadda S, Senthamizhchelvan S, et al. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for PC. Clin Cancer Res. 2011;17:7645–53.PubMedPubMedCentralCrossRef
30.
Cardinale J, Schäfer M, Benešová M, Bauder-Wüst U, Leotta K, Eder M, et al. Preclinical evaluation of 18F-PSMA-1007, a new prostate-specific membrane antigen ligand for prostate cancer imaging. J Nucl Med. 2017;58:425–31.PubMedCrossRef
31.
Giesel FL, Hadaschik B, Cardinale J, Radtke J, Vinsensia M, Lehnert W, et al. 18F labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumour lesions in PC patients. Eur J Nucl Med Mol Imaging. 2017;44:678–88.PubMedCrossRef
32.
Manyak MJ. 111Indium capromab pendetide in the management of recurrent prostate cancer. Expert Rev Anticancer Ther. 2008;8:175–81.PubMedCrossRef
33.
Pandit-Taskar N, O’Donoghue JA, Ruan S, Lyashchenko SK, Carrasquillo JA, Heller G, et al. First-in-human imaging with 89Zr-Df-IAB2M anti-PSMA minibody in patients with mPC: pharmacokinetics, biodistribution, dosimetry, and lesion-uptake. J Nucl Med. 2016;57:1858–64.PubMedPubMedCentralCrossRef
34.
Kozikowski AP, Nan F, Conti P, Zhang J, Ramadan E, Bzdega T, et al. Design of remarkably simple, yet potent urea-based inhibitors of glutamate carboxypeptidase II (NAALADase). J Med Chem. 2001;44:298–301.PubMedCrossRef
35.
Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, et al. The theranostic PSMA ligand PSMA-617 in the diagnosis of PC by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumour lesions. J Nucl Med. 2015;56:1697–705.PubMedCrossRef
36.
Kratochwil C, Bruchertseifer F, Giesel FL, Weis M, Verburg FA, Mottaghy F, et al. 225Ac-PSMA-617 for PSMA-targeted α-radiation therapy of metastatic castration-resistant PC. J Nucl Med. 2016;57:1941–4.
37.
Grubmüller B, Baum RP, Capasso E, Singh A, Ahmadi Y, Knoll P, et al. 64Cu-PSMA-617 PET/CT imaging of prostate adenocarcinoma: first in-human studies. Cancer Biother Radiopharm 2016 7. [Epub ahead of print].
38.
An open-label, single-arm, rater-blinded, multicenter phase ½ study to assess safety and diagnostic accuracy and radiotherapeutic implications of pre-operative Ga-68-PSMA-11 PET/CT imaging in comparison to histopathology, in newly diagnosed prostate cancer (PCA) patients at high risk for metastasis, scheduled for radical prostatectomy (RP) with extended pelvic lymph node dissection (EPLND) EudraCT No.: 2016001815–19.
39.
Sachpekidis C, Kopka K, Eder M, Hadaschik BA, Freitag MT, Pan L, et al. 68Ga-PSMA-11 dynamic PET/CT imaging in primary PC. Clin Nucl Med. 2016;41:e473–9.PubMedCrossRef
40.
Uprimny C, Kroiss AS, Decristoforo C, Fritz J, von Guggenberg E, Kendler D, et al. 68Ga-PSMA-11 PET/CT in primary staging of PC: PSA and GS predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44:941–9.PubMedCrossRef
41.
Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of 68Ga-PSMA PET compared to conventional imaging for LN-staging of 130 consecutive patients with intermediate to high-risk PC. J Urol. 2016;195:1436–43.PubMedCrossRef
42.
Budäus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, et al. Initial experience of 68Ga-PSMA PET/CT imaging in high-risk PC-patients prior to RP. Eur Urol. 2016;69:393–6.PubMedCrossRef
43.
Fanti S, Minozzi S, Morigi JJ, Giesel F, Ceci F, Uprimny C, et al. Development of standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent lesions. Eur J Nucl Med Mol Imaging 2017 23.
44.
van Leeuwen PJ, Emmett L, Ho B, Delprado W, Ting F, Nguyen Q, et al. Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative LN-staging in PC. BJU Int. 2017;119:209–15.PubMedCrossRef
45.
Herlemann A, Wenter V, Kretschmer A, Thierfelder KM, Bartenstein P, Faber C, et al. 68Ga-PSMA positron emission tomography/computer tomography provides accurate staging of LN-regions prior to LN-dissection in patients with PC. Eur Urol. 2016;70:553–7.PubMedCrossRef
46.
Demirkol MO, Acar Ö, Uçar B, Ramazanoğlu SR, Sağlıcan Y, Esen T. Prostate-specific membrane antigen-based imaging in PC: impact on clinical decision making process. Prostate. 2015;75:748–57.PubMedCrossRef
47.
Sterzing F, Kratochwil C, Fiedler H, Katayama S, Habl G, Kopka K, et al. 68Ga-PSMA-11 PET/CT: a new technique with high potential for the radiotherapeutic management of PC patients. Eur J Nucl Med Mol Imaging. 2016;43:34–41.PubMedCrossRef
48.
Sahlmann CO, Meller B, Bouter C, Ritter CO, Ströbel P, Lotz J, et al. Biphasic 68Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk PC. Eur J Nucl Med Mol Imaging. 2016;43:898–905.PubMedCrossRef
49.
Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive 68Ga-PSMA-PET in advanced PC: a systematic review and meta-analysis. Eur Urol. 2016;70:926–37.PubMedCrossRef
50.
Ceci F, Uprimny C, Nilica B, Geraldo L, Kendler D, Kroiss A, et al. 68Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging. 2015;42:1284–94.PubMedCrossRef
51.
Verburg FA, Pfister D, Heidenreich A, Vogg A, Drude NI, Vöö S, et al. Extent of disease in recurrent prostate cancer determined by [68Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and GS. Eur J Nucl Med Mol Imaging. 2016;43:397–403.PubMedCrossRef
52.
Schiavina R, Ceci F, Romagnoli D, Uprimny C, Brunocilla E, Borghesi M, et al. 68Ga-PSMA-PET/CT-guided salvage retroperitoneal LN-dissection for disease relapse after radical prostatectomy for PC. Clin Genitourin Cancer. 2015;13:e415–7.PubMedCrossRef
53.
van Leeuwen PJ, Stricker P, Hruby G, Kneebone A, Ting F, Thompson B, et al. 68Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU Int. 2016;117:732–9.PubMedCrossRef
54.
Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209.PubMedCrossRef
55.
Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017;44:1258–68.PubMedPubMedCentralCrossRef
56.
Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with BR after RP. J Nucl Med. 2015;56:668–74.PubMedCrossRef
57.
Einspieler I, Ruascher I, Düwel C, Krönke M, Rischpler C, Habl G, et al. Detection efficacy of hybrid 68Ga-PSMA ligand PET/CT in PC-patients with biochemical recurrence after primary radiation therapy defined by phoenix criteria. J Nucl Med. 2017;58:1081–7.PubMedCrossRef
58.
Kabasakal L, Demirci E, Nematyazar J, Akyel R, Razavi B, Ocak M, et al. The role of PSMA PET/CT imaging in restaging PC patients with low prostate-specific antigen levels. Nucl Med Commun. 2017;38:149–55.PubMedCrossRef
59.
Sachpekidis C, Eder M, Kopka K, Mier W, Hadaschik BA, Haberkorn U, et al. 68Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of PC. Eur J Nucl Med Mol Imaging. 2016;43:1288–99.PubMedCrossRef
60.
Hövels AM, Heesakkers RA, Adang EM, Jager GJ, Jager GJ, Strum S, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic LN in patients with PC: a meta-analysis. Clin Radiol. 2008;63:387–95.PubMedCrossRef
61.
Rauscher I, Maurer T, Beer AJ, Graner FP, Haller B, Weirich G, et al. Value of 68Ga-PSMA HBED-CC for the assessment of LN metastases in PC-patients with BR: comparison with histopathology after salvage lymphadenectomy. J Nucl Med. 2016;57:1713–9.PubMedCrossRef
62.
Albisinni S, Artigas C, Aoun F, Biaou I, Grosman J, Gil T, et al. Clinical impact of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer with rising prostate-specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach. BJU Int. 2017;120:197–203.PubMedCrossRef
63.
Lütje S, Blex S, Gomez B, Schaarschmidt BM, Umutlu L, Forsting M, et al. Optimization of acquisition time of 68Ga-PSMA-ligand PET/MRI in patients with local and mPC. PLoS One. 2016;11:e0164392.PubMedPubMedCentralCrossRef
64.
Noto B, Büther F, Auf der Springe K, Avramovic N, Heindel W, Schäfers M, et al. Impact of PET acquisition durations on image quality and lesion detectability in whole-body 68Ga-PSMA PET/MRI. EJNMMI Res. 2017;7:–12.
65.
Afshar-Oromieh A, Wolf M, Haberkorn U, Kachelrieß M, Gnirs R, Kopka K, et al. Effects of arm truncation on the appearance of the halo artifact in 68Ga-PSMA-11 (HBED-CC) PET/MRI. Eur J Nucl Med Mol Imaging 2017 15.
66.
Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I, et al. Simultaneous 68Ga-PSMA HBED-CC PET/mpMRI improves the localization of primary PC. Eur Urol. 2016;70:829–36.PubMedCrossRef
67.
68.
Giesel FL, Sterzing F, Schlemmer HP, Holland-Letz T, Mier W, Rius M, et al. Intra-individual comparison of 68Ga-PSMA-11-PET/CT and multi-parametric MR for imaging of primary prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:1400–6.PubMedPubMedCentralCrossRef
69.
Zamboglou C, Drendel V, Jilg CA, Rischke HC, Beck TI, Schultze-Seemann W, et al. Comparison of 68Ga-HBED-CC PSMA-PET/CT and multiparametric MRI for gross tumour volume detection in patients with primary PC based on slice by slice comparison with histopathology. Theranostics. 2017;7:228–37.PubMedPubMedCentralCrossRef
70.
Zamboglou C, Wieser G, Hennies S, Rempel I, Kirste S, Soschynski M, et al. MRI versus 68Ga-PSMA PET/CT for gross tumour volume delineation in radiation treatment planning of primary prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:889–97.PubMedCrossRef
71.
Iagaru A. 68Ga-PSMA PET/MRI for detection of regional nodal and distant metastases in patients with intermediate and high-risk PC. [PROS0075; NCT02678351]. Anco Fax News. 2016;15:8.
72.
Kranzbühler B, Nagel H, Becker AS, Müller J, Huellner M, Stolzmann P, et al. Clinical performance of 68Ga-PSMA-11 PET/MRI for the detection of recurrent prostate cancer following radical prostatectomy. Eur J Nucl Med Mol Imaging 2018;45(1):20–30.
73.
Freitag MT, Radtke JP, Hadaschik BA, Kopp-Schneider A, Eder M, Kopka K, et al. Comparison of hybrid 68Ga-PSMA PET/MRI and 68Ga-PSMA PET/CT in the evaluation of LN- and bone metastases of PC. Eur J Nucl Med Mol Imaging. 2016;43:70–83.PubMedCrossRef
74.
Freitag MT, Radtke JP, Afshar-Oromieh A, Roethke MC, Hadaschik BA, Gleave M, et al. Local recurrence of PC after RP is at risk to be missed in 68Ga-PSMA-11-PET of PET/CT and PET/MRI: comparison with mpMRI integrated in simultaneous PET/MRI. Eur J Nucl Med Mol Imaging. 2017;44:776–87.PubMedCrossRef
75.
Maurer T, Beck V, Beer A, Souvatzoglou M, Holzapfel K, Kübler H, et al. Detection rates of 68Ga-labelled ligand of PSMA PET/CT and PET/MRI in 332 consecutive patients with biochemical recurrency after RP. J Urol. 2015;193(Suppl):4.
76.
Castellucci P, Fuccio C, Nanni C, Santi I, Rizzello A, Lodi F, et al. Influence of trigger PSA and PSA kinetics on 11C-Choline PET/CT detection rate in patients with biochemical relapse after radical prostatectomy. J Nucl Med. 2009;50:1394–400.PubMedCrossRef
77.
Graziani T, Ceci F, Castellucci P, Polverari G, Lima GM, Lodi F, et al. 11C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series. Eur J Nucl Med Mol Imaging. 2016;43:1971–9.PubMedCrossRef
78.
Fanti S, Minozzi S, Castellucci P, Balduzzi S, Herrmann K, Krause BJ, et al. PET/CT with 11C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data. Eur J Nucl Med Mol Imaging. 2016;43:55–69.PubMedCrossRef
79.
Evangelista L, Guttilla A, Zattoni F, Zattoni F. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk PC: a systematic literature review and meta-analysis. Eur Urol. 2013;63:1040–8.PubMedCrossRef
80.
Pfister D, Porres D, Heidenreich A, Heidegger I, Knuechel R, Steib F, et al. Detection of recurrent PC-lesions before salvage lymphadenectomy is more accurate with 68Ga-PSMA-HBED-CC than with 18F-fluoroethylcholine PET/CT. Eur J Nucl Med Mol Imaging. 2016;43:1410–7.PubMedCrossRef
81.
Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, et al. Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:11–20.PubMedCrossRef
82.
Bluemel C, Krebs M, Polat B, Linke F, Eiber M, Samnick S, et al. 68Ga-PSMA-PET/CT in patients with biochemical prostate cancer recurrence and negative 18F-choline-PET/CT. Clin Nucl Med. 2016;41:515–21.PubMedPubMedCentralCrossRef
83.
von Eyben FE, Picchio M, von Eyben R, Rhee H, Bauman G. 68Ga-labeled prostate-specific membrane antigen ligand positron emission tomography/computed tomography for PC: a systematic review and meta-analysis. Eur Urol Focus. 2016.
84.
Giovacchini G, Giovannini E, Leoncini R, Riondato M, Ciarmiello A. PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies. Eur J Nucl Med Mol Imaging. 2017; 44(10):1751–76.
85.
Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in PC-patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015;56:1185–90.PubMedCrossRef
86.
Afshar-Oromieh A, Sattler LP, Mier W, Hadaschik BA, Debus J, Holland-Letz T, et al. The clinical impact of additional late PET/CT imaging with 68Ga-PSMA-11 (HBED-CC) in the diagnosis of PC. J Nucl Med. 2017;58:750–5.PubMedCrossRef
87.
Schmuck S, Nordlohne S, von Klot CA, Henkenberens C, Sohns JM, Christiansen H, et al. Comparison of standard and delayed imaging to improve the detection rate of [68Ga]PSMA I&T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for PC. Eur J Nucl Med Mol Imaging. 2017;44:960–8.PubMedCrossRef
88.
Uprimny C, Kroiss AS, Decristoforo C, Fritz J, Warwitz B, Scarpa L, et al. Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and PC-lesions. Eur J Nucl Med Mol Imaging. 2017;44:765–75.PubMedCrossRef
89.
Kabasakal L, Demirci E, Ocak M, Akyel R, Nematyazar J, Aygun A, et al. Evaluation of PSMA PET/CT imaging using a 68Ga-HBED-CC ligand in patients with PC and the value of early pelvic imaging. Nucl Med Commun. 2015;36:582–7.PubMedCrossRef
90.
Fendler WP, Calais J, Allen-Auerbach M, Bluemel C, Eberhardt N, Emmett L, et al. 68Ga-PSMA-11 PET/CT interobserver agreement for PC-assessments: an international multicenter prospective study. J Nucl Med 2017; 58(10):1617–23.
91.
Wright GL Jr, Grob BM, Haley C, Grossman K, Newhall K, Petrylak D, et al. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology. 1996;48:326–34.PubMedCrossRef
92.
Hope TA, Truillet C, Ehman EC, Afshar-Oromieh A, Aggarwal R, Ryan CJ, et al. 68Ga-PSMA-11 PET imaging of response to androgen receptor inhibition: first human experience. J Nucl Med. 2017;58:81–4.PubMedPubMedCentralCrossRef
93.
Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3:81–5.PubMed
94.
Chang SS, O’Keefe DS, Bacich DJ, Reuter VE, Heston WD, Gaudin PB. Prostate-specific membrane antigen is produced in tumour-associated neovasculature. Clin Cancer Res. 1999;5:2674–81.PubMed
95.
Krohn T, Verburg FA, Pufe T, Neuhuber W, Vogg A, Heinzel A, et al. [68Ga]PSMA-HBED uptake mimicking LN-metastasis in coeliac ganglia: an important pitfall in clinical practice. Eur J Nucl Med Mol Imaging. 2015;42:210–4.PubMedCrossRef
96.
Beauregard JM, Hofman MS, Kong G, Hicks RJ. The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging. 2012;39:50–6.PubMedCrossRef
97.
Pandey MK, Byrne JF, Jiang H, Packard AB, DeGrado TR. Cyclotron production of 68Ga via the 68Zn(p,n)68Ga reaction in aqueous solution. Am J Nucl Med Mol Imaging. 2014;4:303–10.PubMedPubMedCentral
98.
Kelly J, Amor-Coarasa A, Nikolopoulou A, Kim D, Williams C Jr, Ponnala S, et al. Synthesis and pre-clinical evaluation of a new class of high-affinity 18F-labeled PSMA ligands for detection of PC by PET imaging. Eur J Nucl Med Mol Imaging. 2017;44:647–61.PubMedCrossRef
99.
Li X, Rowe SP, Leal JP, Gorin MA, Allaf ME, Ross AE, et al. Semiquantitative parameters in PSMA-targeted PET-imaging with 18F-DCFPyL: variability in normal-organ uptake. J Nucl Med. 2017;58:942–6.PubMedPubMedCentralCrossRef
100.
Dietlein F, Kobe C, Neubauer S, Schmidt M, Stockter S, Fischer T, et al. PSA-stratified performance of 18F- and 68Ga-PSMA PET in patients with biochemical recurrence of prostate cancer. J Nucl Med. 2017;58:947–52.PubMedCrossRef
101.
Kesch C, Vinsensia M, Radtke JP, Schlemmer HP, Heller M, Ellert E, et al. Intra-individual comparison of 18F-PSMA-1007-PET/CT, multi-parametric MRI and radical prostatectomy specimen in patients with primary PC—a retrospective, proof of concept study. J Nucl Med. 2017;58(11):1805–10.
102.
Giesel FL, Cardinale J, Schäfer M, Neels O, Benešová M, Mier W, et al. 18F-labelled PSMA-1007 shows similarity in structure, biodistribution and tumour uptake to the theragnostic compound PSMA-617. Eur J Nucl Med Mol Imaging. 2016;43:1929–30.PubMedPubMedCentralCrossRef
103.
Gorin MA, Rowe SP, Mana-ay M, et al. Study of PSMA-targeted 18F-DCFPyL PET/CT in the evaluation of men with an elevated PSA following RP. J Urol. 2016;195(suppl 4):e679–80.CrossRef
104.
Cantiello F, Gangemi V, Cascini GL, Calabria F, Moschini M, Ferro M, et al. Diagnostic accuracy of 64copper prostate-specific membrane antigen positron emission tomography/computed tomography for primary LN-staging of intermediate- to high-risk PC: our preliminary experience. Urology 2017;105:139–145.
105.
Krause BJ, Souvatzoglou M, Tuncel M, Herrmann K, Buck AK, Praus C, et al. The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with BR of PC. Eur J Nucl Med Mol Imaging. 2008;35:18–23.PubMedCrossRef
106.
Picchio M, Spinapolice EG, Fallanca F, Crivellaro C, Giovacchini G, Gianolli L, et al. [11C]Choline PET/CT detection of bone metastases in patients with PSA progression after primary treatment for prostate cancer: comparison with bone scintigraphy. Eur J Nucl Med Mol Imaging. 2012;39:13–26.PubMedCrossRef
107.
Mamede M, Ceci F, Castellucci P, Schiavina R, Fuccio C, Nanni C, et al. The role of 11C-choline PET imaging in the early detection of recurrence in surgically treated prostate cancer patients with very low PSA level <0.5 ng/mL. Clin Nucl Med. 2013;38(9):e342–5.PubMedCrossRef
108.
Passoni NM, Suardi N, Abdollah F, Picchio M, Giovacchini G, Messa C, et al. Utility of [11C]choline PET/CT in guiding lesion-targeted salvage therapies in patients with prostate cancer recurrence localized to a single lymph node at imaging: results from a pathologically validated series. Urol Oncol. 2014 Jan;32(1):38.e9–16.CrossRef
109.
Mitchell CR, Lowe VJ, Rangel LJ, Hung JC, Kwon ED, Karnes RJ. Operational characteristics of 11C-choline positron emission tomography/computerized tomography for prostate cancer with biochemical recurrence after initial treatment. J Urol. 2013;189:1308–13.PubMedCrossRef
110.
Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on PC. Part II: treatment of relapsing, metastatic, and CRPC. Eur Urol. 2017;71:630–42.PubMedCrossRef
111.
Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, et al. Lutetium-177 PSMA radioligand therapy of mCRPC: safety and efficacy. J Nucl Med. 2016;57:1006–13.PubMedCrossRef
112.
Kulkarni HR, Singh A, Schuchardt C, Niepsch K, Sayeg M, Leshch Y, et al. PSMA-based radioligand therapy for mCRPC: the Bad Berka experience since 2013. J Nucl Med. 2016;57:97S–104S.PubMedCrossRef
113.
Rahbar K, Ahmadzadehfar H, Kratochwil C, Haberkorn U, Schäfers M, Essler M, et al. German multicenter study investigating 177Lu-PSMA-617 radioligand therapy in advanced PC-patients. J Nucl Med. 2017;58:85–90.PubMedCrossRef
114.
Rahbar K, Schmidt M, Heinzel A, Eppard E, Bode A, Yordanova A, et al. Response and tolerability of a single activity of 177Lu-PSMA-617 in patients with mCRPC: a multicenter retrospective analysis. J Nucl Med. 2016;57:1334–8.PubMedCrossRef
115.
Yadav MP, Ballal S, Tripathi M, Damle NA, Sahoo RK, Seth A, et al. 177Lu-DKFZ-PSMA-617 therapy in mCRPC: safety, efficacy, and quality of life assessment. Eur J Nucl Med Mol Imaging. 2017;44:81–91.PubMedCrossRef
116.
Heck MM, Retz M, D’Alessandria C, Rauscher I, Scheidhauer K, Maurer T, et al. Systemic radioligand therapy with 177Lu-labeled prostate-specific membrane antigen-ligand for imaging and therapy in patients with mCRPC. J Urol. 2016;196:382–91.PubMedCrossRef
117.
Fendler WP, Reinhardt S, Ilhan H, Delker A, Böning G, Gildehaus FJ, et al. Preliminary experience with dosimetry, response and patient reported outcome after 177Lu-PSMA-617 therapy for mCRPC. Oncotarget. 2017;8:3581–90.PubMedCrossRef
118.
Scarpa L, Buxbaum S, Kendler D, Fink K, Bektic J, Gruber L, et al. The 68Ga/177Lu theragnostic concept in PSMA targeting of CRPC: correlation of SUVmax values and absorbed activity estimates. Eur J Nucl Med Mol Imaging. 2017;44:788–800.PubMedCrossRef
119.
Kratochwil C, Giesel FL, Stefanova M, Benešová M, Bronzel M, Afshar-Oromieh A, et al. PSMA-targeted radionuclide therapy of mCRPC with 177Lu-labeled PSMA-617. J Nucl Med. 2016;57:1170–6.PubMedCrossRef
120.
Ahmadzadehfar H, Eppard E, Kürpig S, Fimmers R, Yordanova A, Schlenkhoff CD, et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of mCRPC. Oncotarget. 2016;7:12477–88.PubMedPubMedCentralCrossRef
121.
Ahmadzadehfar H, Wegen S, Yordanova A, Fimmers R, Kürpig S, Eppard E, et al. Overall survival and response pattern of mCRPC to multiple cycles of radioligand therapy using 177Lu-PSMA-617. Eur J Nucl Med Mol Imaging. 2017;44:1448–54.PubMedCrossRef
122.
Yordanova A, Becker A, Eppard E, Kürpig S, Fisang C, Feldmann G, et al. The impact of repeated cycles of radioligand therapy using 177Lu-PSMA-617 on renal function in patients with hormone refractory mPC. Eur J Nucl Med Mol Imaging. 2017;44:1473–9.PubMedCrossRef
123.
124.
Ahmadzadehfar H, Zimbelmann S, Yordanova A, Fimmers R, Kürpig S, Eppard E, et al. Radioligand therapy of metastatic prostate cancer using 177Lu-PSMA-617 after radiation exposure to 223Ra-dichloride. Oncotarget 2017. [Epub ahead of print].
125.
Tesson M, Rae C, Nixon C, Babich JW, Mairs RJ. Preliminary evaluation of prostate-targeted radiotherapy using 131I-MIP-1095 in combination with radiosensitising chemotherapeutic drugs. J Pharm Pharmacol. 2016;68:912–21.PubMedPubMedCentralCrossRef
126.
Afshar-Oromieh A, Haberkorn U, Zechmann C, Armor T, Mier W, Spohn F, et al. Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with 131I-MIP-1095. Eur J Nucl Med Mol Imaging. 2017;44:950–9.PubMedPubMedCentralCrossRef
127.
Kiess AP, Minn I, Chen Y, Hobbs R, Sgouros G, Mease RC, et al. Auger radiopharmaceutical therapy targeting prostate-specific membrane antigen. J Nucl Med. 2015;56:1401–7.PubMedPubMedCentralCrossRef
128.
Kiess A, Minn IL, Vaidyanathan G, Hobbs RF, Josefsson A, Shen C, et al. (2S)-2-(3-(1-Carboxy-5-(4-211At-astatobenzamido)pentyl)ureido)-pentanedioic acid for PSMA-targeted α-particle radiopharmaceutical therapy. J Nucl Med. 2016;57:1569–75.PubMedPubMedCentralCrossRef
129.
Kratochwil C, Bruchertseifer F, Rathke H, Bronzel M, Apostolidis C, Weichert W, et al. Targeted alpha therapy of mCRPC with 225Actinium-PSMA-617: dosimetry estimate and empirical activity finding. J Nucl Med. 2017;58:1624–31.PubMedCrossRef
130.
Sathekge M, Knoesen O, Meckel M, Modiselle M, Vorster M, Marx S. 213Bi-PSMA-617 targeted alpha-radionuclide therapy in mCRPC. Eur J Nucl Med Mol Imaging. 2017;44:1099–100.PubMedPubMedCentralCrossRef
131.
World Medical Association. World medical association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4.CrossRef
132.
Kabasakal L, AbuQbeitah M, Aygün A, Yeyin N, Ocak M, Demirci E, et al. Pre-therapeutic dosimetry of normal organs and tissues of 177Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with CRPC. Eur J Nucl Med Mol Imaging. 2015;42:1976–83.PubMedCrossRef
133.
Kratochwil C, Giesel FL, Leotta K, Eder M, Hoppe-Tich T, Youssoufian H, et al. PMPA for nephroprotection in PSMA-targeted radionuclide therapy of PC. J Nucl Med. 2015;56:293–8.PubMedCrossRef
134.
Okamoto S, Thieme A, Allmann J, D’Alessandria C, Maurer T, Retz M, et al. Radiation dosimetry for 177Lu-PSMA-I&T in mCRPC: absorbed activity in normal organs and tumour lesions. J Nucl Med. 2017;58:445–50.PubMedCrossRef
135.
Bohn KP, Kletting P, Solbach C, Beer AJ, Krohn T, Effekt der Kühlung v. Speicheldrüsen bei der Therapie mit PSMA-Radioliganden. Nuklearmedizin. 2017;56:A2–A91.
136.
Li Y, Taylor JMG, Ten Haken RK, Eisbruch A. The impact of activity on parotid salivary recovery in head and neck cancer patients treated with radiation therapy. Int J Radiat Oncol Biol Phys. 2007;67:660–9.PubMedCrossRef
137.
Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–22.PubMedCrossRef
138.
Kratochwil C, Giesel FL, Eder M, Afshar-Oromieh A, Benešová M, Mier W, et al. 177Lu-labelled PSMA ligand-induced remission in a patient with mPC. Eur J Nucl Med Mol Imaging. 2015;42:987–8.PubMedCrossRef
139.
Ahmadzadehfar H, Rahbar K, Kürpig S, Bögemann M, Claesener M, Eppard E, et al. Early side effects and first results of radioligand therapy with 177Lu-DKFZ-617 PSMA of mCRPC: a two-centre study. EJNMMI Res. 2015;5:114.PubMed
140.
von Eyben FE, Roviello G, Kiljunen T, Uprimny C, Virgolini I, Kairemo K, Joensuu T. Is third-line treatment of metastatic castration-resistant prostate cancer better than 177Lu-PSMA radioligand therapy? A systematic review and meta-analysis. Submitted to EJNMMI.
141.
Fendler WP, Stuparu AD, Evans-Axelsson S, Lückerath K, Wei L, Kim W, et al. Establishing 177Lu-PSMA-617 radioligand therapy in a syngeneic model of murine PC. JNM 2017.
142.
Parker CC, Coleman RE, Sartor O, Vogelzang NJ, Bottomley D, Heinrich D, et al. Three-year safety of 223Ra dichloride in patients with CRPC and symptomatic bone metastases from phase III randomized alpharadin in symptomatic prostate cancer trial. Eur Urol. 2017 Jul 10; https://​doi.​org/​10.​1016/​j.​eururo.​2017.​06.​021. [Epub ahead of print]
143.
Florimonte L, Dellavedova L, Maffioli LS. 223Radium dichloride in clinical practice: a review. Eur J Nucl Med Mol Imaging. 2016;43:1896–909.PubMedCrossRef
144.
ALGETA ASA: Alpharadion ® injection (radium-223 chloride) – Investigator’s brochure, Oslo, Norway Edition No: 7, 15 2010.
145.
Chittenden SJ, Hindorf C, Parker CC, Lewington VJ, Pratt BE, Johnson B, et al. A phase 1, open-label study of the biodistribution, pharmacokinetics, and dosimetry of 223Ra-dichloride in patients with hormone-refractory prostate cancer and skeletal metastases. J Nucl Med. 2015;56:1304–9.PubMedCrossRef
146.
Lassmann M, Nosseke D. Dosimetry of 223Ra-chloride: use to normal organs and tissues. Eur J Nucl Med Mol Imaging. 2013;40:207–12.PubMedCrossRef
147.
ICRP. Age-dependent activities to members of the public from intake of radionuclides: Part 2. Ingestion activity coefficients. A report of a task Group of Committee 2 of the international commission on radiological protection. Ann ICRP. 1993;23:1–167.
148.
Sgourus G, Roeske JC, McDevitt MR, Palm S, Allen BJ, Fisher DR, et al. MIRD pamphlet no.22 (abridged): radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy. J Nucl Med. 2010;51:311–28.CrossRef
Metadata
Title
Current status of theranostics in prostate cancer
Authors
Irene Virgolini
Clemens Decristoforo
Alexander Haug
Stefano Fanti
Christian Uprimny
Publication date
01-03-2018
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3882-2

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