Der Nuklearmediziner 2020; 43(04): 275-288
DOI: 10.1055/a-1108-7061
Uroonkologie

Radiotracer zur Diagnose des Prostatakarzinoms: Etablierte und neue Verfahren

Radiolabeled Tracers for Prostate Cancer Diagnostics: Established and Novel Strategies
Gábor Bakos
1   Deutsches Krebsforschungszentrum (DKFZ), Nachwuchsgruppe Molekularbiologie Systemischer Radiotherapie, Heidelberg
,
Mareike Roscher
2   Deutsches Krebsforschungszentrum (DKFZ), Abteilung Radioonkologie / Radiobiologie, Heidelberg
,
Susana M. Granados
3   Deutsches Krebsforschungszentrum (DKFZ), Klinische Kooperationseinheit Translationale Radioonkologie, Heidelberg
4   Deutsches Krebsforschungszentrum (DKFZ), Klinische Kooperationseinheit Nuklearmedizin, Heidelberg
,
Martina Benešová
1   Deutsches Krebsforschungszentrum (DKFZ), Nachwuchsgruppe Molekularbiologie Systemischer Radiotherapie, Heidelberg
› Author Affiliations

Zusammenfassung

Die nuklearmedizinische Diagnose von Tumoren basierend auf der Radiotracer-vermittelten Bildgebung hat sich in den letzten Jahrzehnten als zentrale Schlüsseltechnologie in der modernen Onkologie etabliert. Die bildgestützte Diagnostik ermöglicht nicht nur die frühe Identifikation und Klassifikation von Tumoren, sondern auch die therapiebegleitende, nicht-invasive Evaluierung des Therapieansprechens sowie der Detektion von Rezidiven, Remissionen und progressiven Erkrankungen nach Abschluss der Therapie. Dies macht die nuklearmedizinische Bildgebung einzigartig im Bereich der personalisierten und Präzisions-Medizin. Daher ist es nur einleuchtend, dass das Feld dynamisch wächst und eine Vielzahl neuer Radiotracer entwickelt werden, die in präklinischen und klinischen Studien validiert werden. In diesem Übersichtsartikel werden die verfügbaren Daten zu den bereits klinisch etablierten metabolischen und zielgerichteten, spezifischen Radiotracern zusammengefasst. Zusätzlich wird ein Ausblick auf neue Entwicklungen gegeben, in dem neue, vielversprechende Radiotracer für die Diagnostik eines Prostatakarzinoms diskutiert werden.

Abstract

In the last decades, radiotracer-based diagnostics emerged as a key tool in modern cancer management. This technique is not only useful for primary diagnosis and staging of tumors, but also enables treatment monitoring as well as early detection and localization of tumor relapse by means of subsequent follow-up examinations. These attributes make radiotracer-based imaging extremely valuable in the current era of personalized and precision medicine. As such it comes as no surprise that this field is dynamically growing, with an increasing number of novel radiotracers and resulting pre-clinical studies as well as clinical trials. In this review, the current knowledge on clinically established metabolic and targeted radiotracers will be summarized and complemented with an outlook on novel, highly potential radiotracers for prostate cancer management.



Publication History

Article published online:
30 November 2020

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  • Literatur

  • 1 Carioli G, Bertuccio P, Boffetta P. et al. European cancer mortality predictions for the year 2020 with a focus on prostate cancer. Ann Oncol 2020; 31: 650-658
  • 2 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70: 7-30
  • 3 Rawla P. Epidemiology of prostate cancer. World J Oncol 2019; 10: 63-89
  • 4 Adekoya TO, Richardson RM. Cytokines and chemokines as mediators of prostate cancer metastasis. Int J Mol Sci 2020; 21: 4449-4478
  • 5 Wang G, Zhao D, Spring DJ. et al. Genetics and biology of prostate cancer. Genes Dev 2018; 32: 1105-1140
  • 6 Perlmutter MA, Lepor H. Androgen deprivation therapy in the treatment of advanced prostate cancer. Rev Urol 2007; 9 (Suppl. 01) S3-S8
  • 7 Wade CA, Kyprianou N. Profiling prostate cancer therapeutic resistance. Int J Mol Sci 2018; 19: 904-923
  • 8 Holm HV, Dahl AA, Klepp OH. et al. Modern treatment of metastatic prostate cancer. Tidsskr Nor Laegeforen 2017; 137: 803-805
  • 9 Nilsson S. Radionuclide therapies in prostate cancer: Integrating radium-223 in the treatment of patients with metastatic castration-resistant prostate cancer. Curr Oncol Rep 2016; 18: 14
  • 10 Logothetis CJ, Gallick GE, Maity SN. et al. Molecular classification of prostate cancer progression: Foundation for marker-driven treatment of prostate cancer. Cancer Discov 2013; 3: 849-861
  • 11 Jadvar H. Molecular imaging of prostate cancer: PET radiotracers. AJR Am J Roentgenol 2012; 199: 278-291
  • 12 Sarkar S, Das S. A review of imaging methods for prostate cancer detection. Biomed Eng Comput Biol 2016; 7: 1-15
  • 13 Rahbar K, Afshar-Oromieh A, Jadvar H. et al. PSMA theranostics: Current status and future directions. Mol Imaging 2018; 17: 1536012118776068
  • 14 Van den Wyngaert T, Elvas F, De Schepper S. et al. SPECT/CT - Standing on the Shoulders of Giants, It Is Time to Reach for the Sky!. J Nucl Med 2020; 61: 1284-1291
  • 15 de Geus-Oei LF, Ruers TJ, Punt CJ. et al. FDG-pet in colorectal cancer. Cancer Imaging 2006; 6: S71-81
  • 16 Wallitt KL, Khan SR, Dubash S. et al. Clinical pet imaging in prostate cancer. Radiographics 2017; 37: 1512-1536
  • 17 Thang SP, Violet J, Sandhu S. et al. Poor outcomes for patients with metastatic castration-resistant prostate cancer with low prostate-specific membrane antigen (PSMA) expression deemed ineligible for (177)Lu-labelled PSMA radioligand therapy. Eur Urol Oncol 2019; 2: 670-676
  • 18 Hedtke V, Bakovic M. Choline transport for phospholipid synthesis: An emerging role of choline transporter-like protein 1. Exp Biol Med (Maywood) 2019; 244: 655-662
  • 19 Witney TH, Alam IS, Turton DR. et al. Evaluation of deuterated 18F- and 11C-labeled choline analogs for cancer detection by positron emission tomography. Clin Cancer Res 2012; 18: 1063-1072
  • 20 Brogsitter C, Zophel K, Kotzerke J. 18F-Choline, 11C-Choline and 11C-Acetate PET/CT: Comparative analysis for imaging prostate cancer patients. Eur J Nucl Med Mol Imaging 2013; 40 (Suppl. 01) S18-S27
  • 21 Massaro A, Cittadin S, Milan E. et al. Optimizing the acquisition protocol of 18F-Choline PET/CT in prostate cancer patients. N Am J Med Sci 2012; 4: 416-420
  • 22 Beheshti M, Rezaee A, Geinitz H. et al. Evaluation of prostate cancer bone metastases with 18F-NaF and 18F-Fluorocholine PET/CT. J Nucl Med 2016; 57: 55S-60S
  • 23 Mansi L, Cuccurullo V, Evangelista L. Is radiocholine PET/CT already clinically useful in patients with prostate cancer?. J Nucl Med 2014; 55: 1401-1403
  • 24 Sakata T, Ferdous G, Tsuruta T. et al. L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathol Int 2009; 59: 7-18
  • 25 Okudaira H, Shikano N, Nishii R. et al. Putative transport mechanism and intracellular fate of trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid in human prostate cancer. J Nucl Med 2011; 52: 822-829
  • 26 Savir-Baruch B, Zanoni L, Schuster DM. Imaging of prostate cancer using fluciclovine. Urol Clin North Am 2018; 45: 489-502
  • 27 Lukey MJ, Katt WP, Cerione RA. Targeting amino acid metabolism for cancer therapy. Drug Discov Today 2017; 22: 796-804
  • 28 England JR, Paluch J, Ballas LK. et al. 18F-Fluciclovine PET/CT detection of recurrent prostate carcinoma in patients with serum PSA ≤ 1 ng/ml after definitive primary treatment. Clin Nucl Med 2019; 44: e128-e132
  • 29 Parent EE, Schuster DM. Update on 18F-Fluciclovine PET for prostate cancer imaging. J Nucl Med 2018; 59: 733-739
  • 30 Rasey JS, Grierson JR, Wiens LW. et al. Validation of flt uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. Journal of Nuclear Medicine 2002; 43: 1210-1217
  • 31 Qi S, Zhongyi Y, Yingjian Z. et al. 18F-FLT and 18F-FDG PET/CT in predicting response to chemoradiotherapy in nasopharyngeal carcinoma: Preliminary results. Sci Rep 2017; 7: 40552
  • 32 Kukuk D, Reischl G, Raguin O. et al. Assessment of PET tracer uptake in hormone-independent and hormone-dependent xenograft prostate cancer mouse models. J Nucl Med 2011; 52: 1654-1663
  • 33 Oyama N, Hasegawa Y, Kiyono Y. et al. Early response assessment in prostate carcinoma by 18F-Fluorothymidine following anticancer therapy with docetaxel using preclinical tumour models. Eur J Nucl Med Mol Imaging 2011; 38: 81-89
  • 34 Kairemo K, Ravizzini GC, Macapinlac HA. et al. An assessment of early response to targeted therapy via molecular imaging: A pilot study of 3'-deoxy-3'[18F]-Fluorothymidine positron emission tomography 18F-FLT PET/CT in prostate adenocarcinoma. Diagnostics (Basel) 2017; 7: 20-29
  • 35 Tehrani OS, Douglas KA, Lawhorn-Crews JM. et al. Tracking cellular stress with labeled FMAU reflects changes in mitochondrial TK2. Eur J Nucl Med Mol Imaging 2008; 35: 1480-1488
  • 36 Sun H, Sloan A, Mangner TJ. et al. Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer. Eur J Nucl Med Mol Imaging 2005; 32: 15-22
  • 37 Tehrani OS, Muzik O, Heilbrun LK. et al. Tumor imaging using 1-(2'-deoxy-2'-18F-Fluoro-beta-D-arabinofuranosyl)thymine and PET. J Nucl Med 2007; 48: 1436-1441
  • 38 Vaishampayan UN, Tehrani OS, Lawhorn-Crews JM. et al. A pilot trial evaluating zoledronic acid induced changes in [18F]FMAU-positron emission tomography imaging of bone metastases in prostate cancer. Mol Imaging Biol 2017; 19: 810-816
  • 39 Sheikhbahaei S, Jones KM, Werner RA. et al. 18F-NaF-PET/CT for the detection of bone metastasis in prostate cancer: A meta-analysis of diagnostic accuracy studies. Ann Nucl Med 2019; 33: 351-361
  • 40 Mesters JR, Barinka C, Li W. et al. Structure of glutamate carboxypeptidase ii, a drug target in neuronal damage and prostate cancer. EMBO J 2006; 25: 1375-1384
  • 41 Dorff TB, Fanti S, Farolfi A. et al. The evolving role of prostate-specific membrane antigen–based diagnostics and therapeutics in prostate cancer. American Society of Clinical Oncology Educational Book 2019; 39: 321-330
  • 42 Liu H, Moy P, Kim S. et al. Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res 1997; 57: 3629-3634
  • 43 Taneja SS. ProstaScint(R) Scan: Contemporary use in clinical practice. Rev Urol 2004; 6 (Suppl. 10) S19-S28
  • 44 Smith-Jones PM, Vallabhajosula S, Navarro V. et al. Radiolabeled monoclonal antibodies specific to the extracellular domain of prostate-specific membrane antigen: Preclinical studies in nude mice bearing LNCaP human prostate tumor. J Nucl Med 2003; 44: 610-617
  • 45 Bander N. Targeted systemic therapy of prostate cancer with a monoclonal antibody to prostate-specific membrane antigen. Seminars in Oncology 2003; 30: 667-676
  • 46 Pandit-Taskar N, O'Donoghue JA, Morris MJ. et al. Antibody mass escalation study in patients with castration-resistant prostate cancer using 111In-J591: Lesion detectability and dosimetric projections for 90Y radioimmunotherapy. J Nucl Med 2008; 49: 1066-1074
  • 47 Pandit-Taskar N, O'Donoghue JA, Beylergil V. et al. 89Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer. Eur J Nucl Med Mol Imaging 2014; 41: 2093-2105
  • 48 Pandit-Taskar N, O'Donoghue JA, Ruan S. et al. First-in-human imaging with 89Zr-Df-IAB2M anti-PSMA minibody in patients with metastatic prostate cancer: Pharmacokinetics, biodistribution, dosimetry, and lesion uptake. J Nucl Med 2016; 57: 1858-1864
  • 49 Wu AM. Engineered antibodies for molecular imaging of cancer. Methods 2014; 65: 139-147
  • 50 Cimadamore A, Cheng M, Santoni M. et al. New prostate cancer targets for diagnosis, imaging, and therapy: Focus on prostate-specific membrane antigen. Front Oncol 2018; 8: 653
  • 51 Joraku A, Hatano K, Kawai K. et al. Phase I/IIa PET imaging study with 89zirconium labeled anti-PSMA minibody for urological malignancies. Ann Nucl Med 2019; 33: 119-127
  • 52 Debie P, Devoogdt N, Hernot S. Targeted nanobody-based molecular tracers for nuclear imaging and image-guided surgery. Antibodies 2019; 8: 12-33
  • 53 Evazalipour M, D'Huyvetter M, Tehrani BS. et al. Generation and characterization of nanobodies targeting PSMA for molecular imaging of prostate cancer. Contrast Media & Molecular Imaging 2014; 9: 211-220
  • 54 Chatalic KL, Veldhoven-Zweistra J, Bolkestein M. et al. A novel 111In-Labeled anti-prostate-specific membrane antigen nanobody for targeted SPECT/CT imaging of prostate cancer. J Nucl Med 2015; 56: 1094-1099
  • 55 Hillier SM, Maresca KP, Femia FJ. et al. Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Research 2009; 69: 6932-6940
  • 56 Maresca KP, Hillier SM, Femia FJ. et al. A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. J Med Chem 2009; 52: 347-357
  • 57 Chen Y, Pullambhatla M, Foss CA. 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 prostate cancer. Clin Cancer Res 2011; 17: 7645-7653
  • 58 Cho SY, Gage KL, Mease RC. et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2012; 53: 1883-1891
  • 59 Eder M, Schäfer M, Bauder-Wüst U. et al. 68Ga-Complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjugate Chem 2012; 23: 688-697
  • 60 Benešová M, Schäfer M, Bauder-Wüst U. et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med 2015; 56: 914-920
  • 61 Weineisen M, Schottelius M, Simecek J. 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: 1169-1176
  • 62 Szabo Z, Mena E, Rowe SP. et al. Initial evaluation of [18F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Molecular Imaging and Biology 2015; 17: 565-574
  • 63 Cardinale J, Schäfer M, Benešová 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: 425-431
  • 64 Zechmann CM, Afshar-Oromieh A, Armor T. et al. Radiation dosimetry and first therapy results with a 124I/131I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging 2014; 41: 1280-1292
  • 65 von Eyben FE, Roviello G, Kiljunen T. et al. Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: A systematic review. Eur J Nucl Med Mol Imaging 2018; 45: 496-508
  • 66 Schmidkonz C, Cordes M, Beck M. et al. SPECT/CT with the PSMA ligand 99mTc-MIP-1404 for whole-body primary staging of patients with prostate cancer. Clinical Nuclear Medicine 2018; 43: 225-231
  • 67 Coleman RE, Barrett JA, Hussain A. et al. Prostate-specific membrane antigen (PSMA)–targeted imaging of metastatic prostate cancer (PCA) via small molecule inhibitors: Comparison to bone scan, CT/MRI, and 111In capromab. J Clin Oncol 2011; 29: 4658-4658
  • 68 Afshar-Oromieh A, Haberkorn U, Hadaschik B. et al. PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer. Eur J Nucl Med Mol Imaging 2013; 40: 1629-1630
  • 69 Rowe SP, Gage KL, Faraj SF. et al. 18F-DCFBC PET/CT for PSMA-based detection and characterization of primary prostate cancer. Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2015; 56: 1003-1010
  • 70 Rowe SP, Macura KJ, Mena E. et al. PSMA-based [18F]DCFPyL PET/CT is superior to conventional imaging for lesion detection in patients with metastatic prostate cancer. Molecular Imaging and Biology 2016; 18: 411-419
  • 71 Langton-Webster B, Berkman C, Slater J. et al. Development of a novel PSMA-targeted PET imaging agent, CTT1057, for use in prostate cancer. J Nucl Med 2016; 57: 467
  • 72 Giesel FL, Hadaschik B, Cardinale J. et al. F-18 labelled PSMA-1007: Biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients. Eur J Nucl Med Mol Imaging 2017; 44: 678-688
  • 73 Barrett JA, Coleman RE, Goldsmith SJ. et al. First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer. J Nucl Med 2013; 54: 380-387
  • 74 Afshar-Oromieh A, Hetzheim H, Kratochwil C. et al. The theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: Biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med 2015; 56: 1697-1705
  • 75 Schottelius M, Wirtz M, Eiber M. et al. [111In]PSMA-I&T: Expanding the spectrum of PSMA-I&T applications towards SPECT and radioguided surgery. EJNMMI Research 2015; 5: 68
  • 76 Kratochwil C, Giesel FL, Stefanova M. et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med 2016; 57: 1170-1176
  • 77 Meyrick DP, Asokendaran M, Skelly LA. et al. The role of 68Ga-PSMA-I&T PET/CT in the pretreatment staging of primary prostate cancer. Nucl Med Commun 2017; 38: 956-963
  • 78 Eppard E, de la Fuente A, Benešová M. et al. Clinical translation and first in-human use of [44Sc]Sc-PSMA-617 for PET imaging of metastasized castrate-resistant prostate cancer. Theranostics 2017; 7: 4359-4369
  • 79 Schuhmacher J, Matys R, Hauser H. et al. Labeling of monoclonal antibodies with a 67Ga-phenolic aminocarboxylic acid chelate. Eur J Nucl Med 1986; 12: 397-404
  • 80 Zöller M, Schuhmacher J, Reed J. et al. Establishment and characterization of monoclonal antibodies against an octahedral gallium chelate suitable for immunoscintigraphy with PET. J Nucl Med 1992; 33: 1366-1372
  • 81 Afshar-Oromieh A, Malcher A, Eder M. 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: 486-495
  • 82 Afshar-Oromieh A, Haberkorn U, Eder M. et al. [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: Comparison with 18F-FECH. Eur J Nucl Med Mol Imaging 2012; 39: 1085-1086
  • 83 Giesel FL, Kesch C, Yun M. et al. 18F-PSMA-1007 PET/CT detects micrometastases in a patient with biochemically recurrent prostate cancer. Clinical Genitourinary Cancer 2017; 15: e497-e499
  • 84 Ferreira CA, Fuscaldi LL, Townsend DM. et al. Radiolabeled bombesin derivatives for preclinical oncological imaging. Biomed Pharmacother 2017; 87: 58-72
  • 85 Cescato R, Maina T, Nock B. et al. Bombesin receptor antagonists may be preferable to agonists for tumor targeting. J Nucl Med 2008; 49: 318-326
  • 86 Minamimoto R, Sonni I, Hancock S. et al. Prospective evaluation of 68Ga-RM2 PET/MRI in patients with biochemical recurrence of prostate cancer and negative findings on conventional imaging. J Nucl Med 2018; 59: 803-808
  • 87 Ishida S, Andreux P, Poitry-Yamate C. et al. Bioavailable copper modulates oxidative phosphorylation and growth of tumors. Proc Natl Acad Sci USA 2013; 110: 19507-19512
  • 88 Peng F, Lu X, Janisse J. et al. PET of human prostate cancer xenografts in mice with increased uptake of 64CuCl2. J Nucl Med 2006; 47: 1649-1652
  • 89 Cai H, Wu JS, Muzik O. et al. Reduced 64Cu uptake and tumor growth inhibition by knockdown of human copper transporter 1 in xenograft mouse model of prostate cancer. J Nucl Med 2014; 55: 622-628
  • 90 Catalogna G, Talarico C, Dattilo V. et al. The SGK1 kinase inhibitor SI113 sensitizes theranostic effects of the 64CuCl2 in human glioblastoma multiforme cells. Cell Physiol Biochem 2017; 43: 108-119
  • 91 Capasso E, Durzu S, Piras S. et al. Role of 64CuCl2 PET/CT in staging of prostate cancer. Ann Nucl Med 2015; 29: 482-488
  • 92 Piccardo A, Paparo F, Puntoni M. et al. 64CuCl2 PET/CT in prostate cancer relapse. J Nucl Med 2018; 59: 444-451
  • 93 Righi S, Ugolini M, Bottoni G. et al. Biokinetic and dosimetric aspects of 64CuCl2 in human prostate cancer: Possible theranostic implications. EJNMMI Res 2018; 8: 18
  • 94 Paparo F, Peirano A, Matos J. et al. Diagnostic value of retrospectively fused 64CuCl2 PET/MRI in biochemical relapse of prostate cancer: Comparison with fused 18F-Choline PET/MRI, 64CuCl2 PET/CT, 18F-Choline PET/CT, and mpMRI. Abdom Radiol (NY) 2020; 45: 3896-3906
  • 95 Avila-Rodriguez MA, Rios C, Carrasco-Hernandez J. et al. Biodistribution and radiation dosimetry of [64Cu]copper dichloride: First-in-human study in healthy volunteers. EJNMMI Res 2017; 7: 98
  • 96 Guerreiro JF, Alves V, Abrunhosa AJ. et al. Radiobiological characterization of 64CuCl2 as a simple tool for prostate cancer theranostics. Molecules 2018; 23: 2944-2959
  • 97 Bierhaus A, Humpert PM, Morcos M. et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl) 2005; 83: 876-886
  • 98 Palanissami G, Paul SFD. RAGE and its ligands: Molecular interplay between glycation, inflammation, and hallmarks of cancer-a review. Horm Cancer 2018; 9: 295-325
  • 99 Hoppmann S, Haase C, Richter S. et al. Expression, purification and fluorine-18 radiolabeling of recombinant S100 proteins--potential probes for molecular imaging of receptor for advanced glycation endproducts (RAGE) in vivo. Protein Expr Purif 2008; 57: 143-152
  • 100 Hoppmann S, Steinbach J, Pietzsch J. Scavenger receptors are associated with cellular interactions of S100A12 in vitro and in vivo. Int J Biochem Cell Biol 2010; 42: 651-661
  • 101 Wolf S, Haase-Kohn C, Lenk J. et al. Expression, purification and fluorine-18 radiolabeling of recombinant S100A4: A potential probe for molecular imaging of receptor for advanced glycation endproducts in vivo?. Amino Acids 2011; 41: 809-820
  • 102 Konopka CJ, Wozniak M, Hedhli J. et al. Quantitative imaging of the receptor for advanced glycation end-products in prostate cancer. Eur J Nucl Med Mol Imaging 2020; 47: 2562-2576
  • 103 Drake LR, Scott PJH. Targeted nanoparticles for multimodal imaging of the receptor for advanced glycation end-products. Theranostics 2018; 8: 6352-6354
  • 104 Coto-Llerena M, Ercan C, Kancherla V. et al. High expression of FAP in colorectal cancer is associated with angiogenesis and immunoregulation processes. Front Oncol 2020; 10: 979
  • 105 Zhang J, Li S, Zhao Y. et al. Cancer-associated fibroblasts promote the migration and invasion of gastric cancer cells via activating IL-17a/JAK2/STAT3 signaling. Annals of Translational Medicine 2020; 8: 877-877
  • 106 Jia C, Wang G, Wang T. et al. Cancer-associated fibroblasts induce epithelial-mesenchymal transition via the transglutaminase 2-dependent IL-6/IL6R/STAT3 axis in hepatocellular carcinoma. International Journal of Biological Sciences 2020; 16: 2542-2558
  • 107 Lindner T, Loktev A, Giesel F. et al. Targeting of activated fibroblasts for imaging and therapy. EJNMMI Radiopharm Chem 2019; 4: 16
  • 108 Loktev A, Lindner T, Burger EM. et al. Development of fibroblast activation protein-targeted radiotracers with improved tumor retention. J Nucl Med 2019; 60: 1421-1429
  • 109 Giesel FL, Kratochwil C, Lindner T. et al. 68Ga-FAPI PET/CT: Biodistribution and preliminary dosimetry estimate of 2 dota-containing FAP-targeting agents in patients with various cancers. J Nucl Med 2019; 60: 386-392
  • 110 Kratochwil C, Flechsig P, Lindner T. et al. 68Ga-FAPI PET/CT: Tracer uptake in 28 different kinds of cancer. J Nucl Med 2019; 60: 801-805
  • 111 Khreish F, Rosar F, Kratochwil C. et al. Positive FAPI-PET/CT in a metastatic castration-resistant prostate cancer patient with PSMA-negative/FDG-positive disease. Eur J Nucl Med Mol Imaging 2020; 47: 2040-2041
  • 112 Gonias SL, Hu J. Urokinase receptor and resistance to targeted anticancer agents. Front Pharmacol 2015; 6: 154
  • 113 Mahmood N, Mihalcioiu C, Rabbani SA. Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): Diagnostic, prognostic, and therapeutic applications. Front Oncol 2018; 8: 24
  • 114 Baart VM, Houvast RD, de Geus-Oei LF. et al. Molecular imaging of the urokinase plasminogen activator receptor: Opportunities beyond cancer. EJNMMI Res 2020; 10: 87
  • 115 Persson M, Skovgaard D, Brandt-Larsen M. et al. First-in-human uPAR PET: Imaging of cancer aggressiveness. Theranostics 2015; 5: 1303-1316
  • 116 Skovgaard D, Persson M, Brandt-Larsen M. et al. Safety, dosimetry, and tumor detection ability of 68Ga-NOTA-AE105: First-in-human study of a novel radioligand for uPAR PET imaging. J Nucl Med 2017; 58: 379-386
  • 117 Reiter RE, Gu Z, Watabe T. et al. Prostate stem cell antigen: A cell surface marker overexpressed in prostate cancer. Proc Natl Acad Sci USA 1998; 95: 1735-1740
  • 118 Ananias HJ, van den Heuvel MC, Helfrich W. et al. Expression of the gastrin-releasing peptide receptor, the prostate stem cell antigen and the prostate-specific membrane antigen in lymph node and bone metastases of prostate cancer. Prostate 2009; 69: 1101-1108
  • 119 Saeki N, Gu J, Yoshida T. et al. Prostate stem cell antigen: A Jekyll and Hyde molecule?. Clin Cancer Res 2010; 16: 3533-3538
  • 120 Jain A, Lam A, Vivanco I. et al. Identification of an androgen-dependent enhancer within the prostate stem cell antigen gene. Mol Endocrinol 2002; 16: 2323-2337
  • 121 Gu Z, Thomas G, Yamashiro J. et al. Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer. Oncogene 2000; 19: 1288-1296
  • 122 Knowles SM, Tavare R, Zettlitz KA. et al. Applications of immunopet: Using 124I-anti-PSCA A11 minibody for imaging disease progression and response to therapy in mouse xenograft models of prostate cancer. Clin Cancer Res 2014; 20: 6367-6378
  • 123 Knowles SM, Zettlitz KA, Tavare R. et al. Quantitative immunopet of prostate cancer xenografts with 89Zr- and 124I-labeled anti-PSCA A11 minibody. J Nucl Med 2014; 55: 452-459
  • 124 Zettlitz KA, Tsai WK, Knowles SM. et al. Dual-modality immuno-PET and near-infrared fluorescence imaging of pancreatic cancer using an anti-prostate stem cell antigen cys-diabody. J Nucl Med 2018; 59: 1398-1405
  • 125 Tsai WK, Zettlitz KA, Tavare R. et al. Dual-modality immunopet/fluorescence imaging of prostate cancer with an anti-PSCA cys-minibody. Theranostics 2018; 8: 5903-5914
  • 126 Zettlitz KA, Tsai WK, Knowles SM. et al. [89Zr]A2cDb immuno-PET of prostate cancer in a human prostate stem cell antigen knock-in (hPSCA KI) syngeneic model. Mol Imaging Biol 2020; 22: 367-376
  • 127 Grosse-Gehling P, Fargeas CA, Dittfeld C. et al. CD133 as a biomarker for putative cancer stem cells in solid tumours: Limitations, problems and challenges. J Pathol 2013; 229: 355-378
  • 128 Glumac PM, LeBeau AM. The role of CD133 in cancer: A concise review. Clin Transl Med 2018; 7: 18
  • 129 Gaedicke S, Braun F, Prasad S. et al. Noninvasive positron emission tomography and fluorescence imaging of CD133+ tumor stem cells. Proc Natl Acad Sci USA 2014; 111: E692-E701
  • 130 Glumac PM, Gallant JP, Shapovalova M. et al. Exploitation of CD133 for the targeted imaging of lethal prostate cancer. Clin Cancer Res 2020; 26: 1054-1064
  • 131 Kohaar I, Petrovics G, Srivastava S. A rich array of prostate cancer molecular biomarkers: Opportunities and challenges. Int J Mol Sci 2019; 20: 1813-1832
  • 132 Tanase CP, Codrici E, Popescu ID. et al. Prostate cancer proteomics: Current trends and future perspectives for biomarker discovery. Oncotarget 2017; 8: 18497-18512