Neue und bewährte Radiopharmaka für die Diagnostik und Therapie des Prostatakarzinoms

 

 Buy Article Permissions and Reprints

Zusammenfassung

Ziel: In diesem Beitrag wird ein Überblick über den aktuellen Stand der radiopharmazeutischen Forschung in Bezug auf die Entwicklung von Radiopharmaka für die Diagnostik und Therapie des Prostatakarzinoms (PCa) gegeben.

Material und Methode: Hierzu wurden die jüngsten Entwicklungen zusammengestellt und mit besonderem Augenmerk auf die klinische Anwendung am Patienten bewertet und kommentiert.

Ergebnisse: Zahlreiche Radiopharmaka, die seit einiger Zeit für die klinische Positronenemissionstomografie (PET) und Single-Photonen-Emissionstomografie (SPECT) Diagnostik des PCa eingesetzt werden, adressieren PCa-assoziierte metabolische Prozesse mit einer mehr oder minder ausgeprägten Spezifität. Beispiele für diese Gruppe von Radiopharmaka sind [¹⁸F]Fluorid, [¹¹C]Acetat, [¹⁸F]Fluoroethylcholin ([¹⁸F]FEC), [¹⁸F]Fluoromethylcholin ([¹⁸F]FMC) und [¹¹C]Cholin. Einen neuen Tracer dieses Typs stellt die künstliche Aminosäure anti-1-amino-3-[¹⁸F]fluorocyclobutan-1-carbonsäure ([¹⁸F]FACBC) dar. Hierneben werden vornehmlich spezifische Rezeptorliganden, wie 16β-[¹⁸F]fluoro-5α-dihydrotestosteron ([¹⁸F]FDHT), radiomarkierte GRPR-Liganden (Gastrin Releasing Peptide Rezeptor, BB2) und radiomarkierte Antikörper gegen das Prostata-spezifische Membranantigen (PSMA, NAALADase I oder Glutamat-Carboxypeptidase II) sowie PSMA-spezifische Inhibitoren untersucht. Für die Therapie des PCa kommen in jüngster Zeit PSMA-gerichtete Antikörper und Inhibitoren zum Einsatz, während für die Radionuklidtherapie ossärer Metastasen in 2014 [²²³Ra]RaCl₂ (Xofigo) die FDA- und EMA-Zulassung erhielt.

Schlussfolgerungen: Während einige ‚metabolische’ Radiopharmaka nur mäßigen Erfolg in klinischen Studien zeigten, stehen mit den jüngst entwickelten PSMA-Inhibitoren, PSMA-bindenden höhermolekularen Radiopharmaka (Antikörper und deren Fragmente) und GRPR-Liganden besonders aussichtsreiche neue Tracer-Klassen für die Diagnostik und Radionuklidtherapie des PCa zur Verfügung. Trotz der bisher herausragenden Ergebnisse mit PSMA-Inhibitoren werden groß angelegte Vergleichsstudien eine vergleichende Bewertung mit GRPR-Liganden erlauben.

Abstract

Goal: This paper gives an overview of the radiopharmaceutical research in the development of radiopharmaceuticals in diagnosis and therapy of prostate cancer (PCa).

Materials and methods: Recent developments were summarized, evaluated and annotated with respect to clinical application in patients.

Results: In clinical positron-emission tomography (PET) and single-photon-emission computed tomography (SPECT) diagnostics of PCa, a variety of radiopharmaceuticals are addressing metabolic processes with higher or lower specificity. Examples of metabolic radiopharmaceuticals are [¹⁸F]fluoride, [¹¹C]acetate, [¹⁸F]fluoroethylcholine ([¹⁸F]FEC), [¹⁸F]fluoromethylcholine ([¹⁸F]FMC) und [¹¹C]choline. A new metabolic tracer is the artificial amino acid anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid ([¹⁸F]FACBC). Additionally, receptor-specific ligands, such as 16β-[¹⁸F]fluoro-5α-dihydrotestosterone ([¹⁸F]FDHT), radiolabeled GRPR ligands (Gastrin Releasing Peptide, BB2) and radiolabeled antibodies against prostate-specific membrane antigen (PSMA, NAALADase I or glutamate carboxypeptidase II), as well as PSMA-specific inhibitors are under evaluation. Recently, PSMA-directed antibodies and inhibitors were introduced for therapy of PCa, and in 2014 [²²³Ra]RaCl₂ (Xofigo) was approved for radionuclide therapy of bone metastases by the FDA and the EMA.

Conclusion: Whereas some ‚metabolic‘ radiopharmaceuticals revealed moderate success in clinical studies, recently developed PSMA inhibitors, PSMA-directed high molecular weight radiopharmaceuticals (antibodies and antibody fragments) and GRPR ligands represent very promising tracer classes for diagnosis and radionuclide therapy of PCa. The outstanding results with PSMA inhibitors need to be elaborated in a large-scale comparative study to show their clinical potential in comparison to GRPR ligands.

• Literatur

• 1 Afshar-Oromieh A, Avtzi E, Giesel FL et al. The diagnostic value of PET/CT imaging with the Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2014;
  PubMedGoogle Scholar
• 2 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
  CrossrefPubMedGoogle Scholar
• 3 Afshar-Oromieh A, Zechmann CM, Malcher A et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2014; 41: 11-20
  CrossrefPubMedGoogle Scholar
• 4 Akhtar NH, Pail O, Saran A et al. Prostate-specific membrane antigen-based therapeutics. Adv Urol 2012; 2012: 973820
  PubMedGoogle Scholar
• 5 Andriole GL, Crawford ED, Grubb 3rd RL et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. Journal of the National Cancer Institute 2012; 104: 125-132
  CrossrefPubMedGoogle Scholar
• 6 Banerjee SR, Pullambhatla M, Byun Y et al. 68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer. J Med Chem 2010; 53: 5333-5341
  CrossrefPubMedGoogle Scholar
• 7 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
  CrossrefPubMedGoogle Scholar
• 8 Beer M, Montani M, Gerhardt J et al. Profiling gastrin-releasing peptide receptor in prostate tissues: clinical implications and molecular correlates. The Prostate 2012; 72: 318-325
  CrossrefPubMedGoogle Scholar
• 9 Beheshti M, Kunit T, Haim S et al. BAY 1075553 PET-CT for Staging and Restaging Prostate Cancer Patients: Comparison with [F] Fluorocholine PET-CT (Phase I Study). Mol Imaging Biol 2014;
  PubMedGoogle Scholar
• 10 Blau M, Ganatra R, Bender MA. 18F-fluoride for bone imaging. Seminars in Nuclear Medicine 1972; 2: 31-37
  CrossrefPubMedGoogle Scholar
• 11 Bodei LFMNJ, Llull J, Cremonesi M, Martano L. 177Lu-AMBA Bombesin analogue in hormone refractory prostate cancer patients: a phase I escalation study with single-cycle administrations. European Association of Nuclear Medicine 2007; 34: 5221
  PubMedGoogle Scholar
• 12 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
  CrossrefPubMedGoogle Scholar
• 13 Challita-Eid PM, Morrison K, Etessami S et al. Monoclonal antibodies to six-transmembrane epithelial antigen of the prostate-1 inhibit intercellular communication in vitro and growth of human tumor xenografts in vivo. Cancer Res 2007; 67: 5798-5805
  CrossrefPubMedGoogle Scholar
• 14 Chang SS, Reuter VE, Heston WD et al. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res 1999; 59: 3192-3198
  PubMedGoogle Scholar
• 15 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. J Nucl Med 2012; 53: 1883-1891
  CrossrefPubMedGoogle Scholar
• 16 DeGrado TR, Baldwin SW, Wang S et al. Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers. J Nucl Med 2001; 42: 1805-1814
  PubMedGoogle Scholar
• 17 Eder M, Schafer M, Bauder-Wust U et al. Preclinical evaluation of a bispecific low-molecular heterodimer targeting both PSMA and GRPR for improved PET imaging and therapy of prostate cancer. The Prostate 2014; 74: 659-668
  CrossrefPubMedGoogle Scholar
• 18 Eder M, Schafer M, Bauder-Wust U et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 2012; 23: 688-697
  CrossrefPubMedGoogle Scholar
• 19 Fani M, Maecke HR. Radiopharmaceutical development of radiolabelled peptides. Eur J Nucl Med Mol Imaging 2012; 39 (Suppl. 01) S11-S30
  CrossrefPubMedGoogle Scholar
• 20 Foss C, Mease R, Cho S et al. GCPII Imaging and Cancer. Current medicinal chemistry 2012; 19: 1346-1359
  CrossrefPubMedGoogle Scholar
• 21 Fuchs BC, Bode BP. Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime?. Seminars in cancer biology 2005; 15: 254-266
  CrossrefPubMedGoogle Scholar
• 22 Ginj M, Zhang H, Waser B et al. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proceedings of the National Academy of Sciences of the United States of America 2006; 103: 16436-16441
  CrossrefPubMedGoogle Scholar
• 23 Hara T, Bansal A, DeGrado TR. Choline transporter as a novel target for molecular imaging of cancer. Mol Imaging 2006; 5: 498-509
  PubMedGoogle Scholar
• 24 Harrison MR, Wong TZ, Armstrong AJ et al. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease. Cancer management and research 2013; 5: 1-14
  PubMedGoogle Scholar
• 25 Heijnsdijk EAM, Wever EM, Auvinen A et al. Quality-of-Life Effects of Prostate-Specific Antigen Screening. New England Journal of Medicine 2012; 367: 595-605
  CrossrefPubMedGoogle Scholar
• 26 Hessels D, Schalken JA. The use of PCA3 in the diagnosis of prostate cancer. Nature reviews Urology 2009; 6: 255-261
  CrossrefPubMedGoogle Scholar
• 27 Hillier SM, Maresca KP, Lu G et al. 99mTc-labeled small-molecule inhibitors of prostate-specific membrane antigen for molecular imaging of prostate cancer. J Nucl Med 2013; 54: 1369-1376
  CrossrefPubMedGoogle Scholar
• 28 Hofer C, Laubenbacher C, Block T et al. Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy. European urology 1999; 36: 31-35
  PubMedGoogle Scholar
• 29 Honer M, Mu L, Stellfeld T et al. 18F-labeled bombesin analog for specific and effective targeting of prostate tumors expressing gastrin-releasing peptide receptors. J Nucl Med 2011; 52: 270-278
  CrossrefPubMedGoogle Scholar
• 30 Kähkönen E, Jambor I, Kemppainen J et al. In Vivo Imaging of Prostate Cancer Using [68Ga]-Labeled Bombesin Analog BAY86-7548. Clinical Cancer Research 2013;
  PubMedGoogle Scholar
• 31 Kalos M, Askaa J, Hylander BL et al. Prostein expression is highly restricted to normal and malignant prostate tissues. The Prostate 2004; 60: 246-256
  CrossrefPubMedGoogle Scholar
• 32 Kiessling A, Wehner R, Füssel S et al. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer. Cancers 2012; 4: 193-217
  CrossrefPubMedGoogle Scholar
• 33 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
  CrossrefPubMedGoogle Scholar
• 34 Lantry LE, Cappelletti E, Maddalena ME et al. 177Lu-AMBA: Synthesis and characterization of a selective 177Lu-labeled GRP-R agonist for systemic radiotherapy of prostate cancer. J Nucl Med 2006; 47: 1144-1152
  PubMedGoogle Scholar
• 35 Larson SM, Morris M, Gunther I et al. Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. J Nucl Med 2004; 45: 366-373
  PubMedGoogle Scholar
• 36 Laverman P, Sosabowski JK, Boerman OC et al. Radiolabelled peptides for oncological diagnosis. Eur J Nucl Med Mol Imaging 2012; 39 (Suppl. 01) S78-S92
  CrossrefPubMedGoogle Scholar
• 37 Lindhe O, Sun A, Ulin J et al. [(18)F]Fluoroacetate is not a functional analogue of [(11)C]acetate in normal physiology. Eur J Nucl Med Mol Imaging 36: 1453-1459
  PubMedGoogle Scholar
• 38 Liu Y. Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer. Prostate Cancer Prostatic Dis 2006; 9: 230-234
  CrossrefPubMedGoogle Scholar
• 39 Lockman PR, Allen DD. The transport of choline. Drug development and industrial pharmacy 2002; 28: 749-771
  CrossrefPubMedGoogle Scholar
• 40 Maina T, Nock B, Mather S. Targeting prostate cancer with radiolabelled bombesins. Cancer imaging: the official publication of the International Cancer Imaging Society 2006; 6: 153-157
  PubMedGoogle Scholar
• 41 Mansi R, Wang X, Forrer F et al. Evaluation of a 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid–Conjugated Bombesin-Based Radioantagonist for the Labeling with Single-Photon Emission Computed Tomography, Positron Emission Tomography, and Therapeutic Radionuclides. Clinical Cancer Research 2009; 15: 5240-5249
  CrossrefPubMedGoogle Scholar
• 42 Mansi R, Wang X, Forrer F et al. Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours. Eur J Nucl Med Mol Imaging 2011; 38: 97-107
  CrossrefPubMedGoogle Scholar
• 43 Mather SJ, Nock BA, Maina T et al. GRP receptor imaging of prostate cancer using [(99m)Tc]Demobesin 4: a first-in-man study. Mol Imaging Biol 2014; 16: 888-895
  CrossrefPubMedGoogle Scholar
• 44 Mease RC. Radionuclide Based Imgaing of Prostate Cancer. Current Topics in Medicinal Chemistry 2010; 10: 1600-1616
  CrossrefPubMedGoogle Scholar
• 45 Mease RC, Foss CA, Pomper MG. PET Imaging in Prostate Cancer: Focus on Prostate-Specific Membrane Antigen. Current topics in medicinal chemistry 2013; 13: 951-962
  CrossrefPubMedGoogle Scholar
• 46 Mohammed A. Biomarkers in prostate cancer: new era and prospective. Med Oncol 2014; 31: 1-6
  PubMedGoogle Scholar
• 47 Nock B, Nikolopoulou A, Chiotellis E et al. [99mTc]Demobesin 1, a novel potent bombesin analogue for GRP receptor-targeted tumour imaging. Eur J Nucl Med Mol Imaging 2003; 30: 247-258
  CrossrefPubMedGoogle Scholar
• 48 Nock BA, Nikolopoulou A, Galanis A et al. Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study. J Med Chem 2005; 48: 100-110
  CrossrefPubMedGoogle Scholar
• 49 Nomura N, Pastorino S, Jiang P et al. Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer cell international 2014; 14: 26
  CrossrefPubMedGoogle Scholar
• 50 Ohnona J, Michaud L, Balogova S et al. Can we achieve a radionuclide radiation dose equal to or less than that of 99mTc-hydroxymethane diphosphonate bone scintigraphy with a low-dose 18 F-sodium fluoride time-of-flight PET of diagnostic quality?. Nuclear medicine communications 2013; 34: 417-425
  CrossrefPubMedGoogle Scholar
• 51 Oka S, Hattori R, Kurosaki F et al. A preliminary study of anti-1-amino-3-18F-fluorocyclobutyl-1-carboxylic acid for the detection of prostate cancer. J Nucl Med 48: 46-55
  PubMedGoogle Scholar
• 52 Olson WC, Heston WD, Rajasekaran AK. Clinical trials of cancer therapies targeting prostate-specific membrane antigen. Reviews on recent clinical trials 2 2007; 2: 182-190
  PubMedGoogle Scholar
• 53 Pandit-Taskar N, O’Donoghue JA, Beylergil V et al. (8)(9)Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer. Eur J Nucl Med Mol Imaging 2014; 41: 2093-2105
  CrossrefPubMedGoogle Scholar
• 54 Pandit-Taskar N, O’Donoghue JA, Beylergil V et al. (89)Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer. Eur J Nucl Med Mol Imaging 2014; 41: 2093-2105
  CrossrefPubMedGoogle Scholar
• 55 Parry R, Schneider D, Hudson D et al. Identification of a novel prostate tumor target, mindin/RG-1, for antibody-based radiotherapy of prostate cancer. Cancer Res 2005; 65: 8397-8405
  CrossrefPubMedGoogle Scholar
• 56 Pillarsetty N, Punzalan B, Larson SM. 2-18F-Fluoropropionic acid as a PET imaging agent for prostate cancer. J Nucl Med 2009; 50: 1709-1714
  CrossrefPubMedGoogle Scholar
• 57 Ponde DE, Dence CS, Oyama N et al. 18F-fluoroacetate: a potential acetate analog for prostate tumor imaging–in vivo evaluation of 18F-fluoroacetate versus 11C-acetate. J Nucl Med 2007; 48: 420-428
  PubMedGoogle Scholar
• 58 Ristau BT, O’Keefe DS, Bacich DJ. The prostate-specific membrane antigen: lessons and current clinical implications from 20 years of research. Urologic oncology 2014; 32: 272-279
  CrossrefPubMedGoogle Scholar
• 59 Schaefer N, Valencia R, Borkowski S et al. Comparison of BAY 86-4367, a new F-18 labeled bombesin analog, with F-18-ethyl-choline in recurrent and primary prostate cancer patients. Journal of Nuclear Medicine 2011; 52: 40
  CrossrefPubMedGoogle Scholar
• 60 Schoder H, Herrmann K, Gonen M et al. 2-[18F]fluoro-2-deoxyglucose positron emission tomography for the detection of disease in patients with prostate-specific antigen relapse after radical prostatectomy. Clin Cancer Res 2005; 11: 4761-4769
  CrossrefPubMedGoogle Scholar
• 61 Schröder FH, Hugosson J, Roobol MJ et al. Screening and Prostate-Cancer Mortality in a Randomized European Study. New England Journal of Medicine 2009; 360: 1320-1328
  CrossrefPubMedGoogle Scholar
• 62 Shreve PD, Grossman HB, Gross MD et al. Metastatic prostate cancer: initial findings of PET with 2-deoxy-2-[F-18]fluoro-D-glucose. Radiology 1996; 199: 751-756
  CrossrefPubMedGoogle Scholar
• 63 Silver DA, Pellicer I, Fair WR et al. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997; 3: 81-85
  PubMedGoogle Scholar
• 64 Slaets D, De Bruyne S, Dumolyn C et al. Reduced dimethylaminoethanol in [(18)F]fluoromethylcholine: an important step towards enhanced tumour visualization. Eur J Nucl Med Mol Imaging 2010; 37: 2136-2145
  CrossrefPubMedGoogle Scholar
• 65 Sokoloff RL, Norton KC, Gasior CL et al. A dual-monoclonal sandwich assay for prostate-specific membrane antigen: levels in tissues, seminal fluid and urine. The Prostate 2000; 43: 150-157
  CrossrefPubMedGoogle Scholar
• 66 Stone NN, Crawford ED. To screen or nor to screen: the prostate cancer dilemma. Asian journal of andrology 2015; 17: 44-45
  CrossrefPubMedGoogle Scholar
• 67 Tagawa ST, Beltran H, Vallabhajosula S et al. Anti–prostate-Specific membrane antigen-based radioimmunotherapy for prostate cancer. Cancer 2010; 116: 1075-1083
  CrossrefPubMedGoogle Scholar
• 68 Tomaszewski JJ, Cummings JL, Parwani AV et al. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate. The Prostate 2011; 71: 1287-1293
  PubMedGoogle Scholar
• 69 Troyer JK, Beckett ML, Wright Jr GL. Location of prostate-specific membrane antigen in the LNCaP prostate carcinoma cell line. The Prostate 1997; 30: 232-242
  CrossrefPubMedGoogle Scholar
• 70 Troyer JK, Feng Q, Beckett ML et al. Biochemical characterization and mapping of the 7E11-C5.3 epitope of the prostate-specific membrane antigen. Urologic oncology 1995; 1: 29-37
  CrossrefPubMedGoogle Scholar
• 71 Turkbey B, Mena E, Shih J et al. Localized prostate cancer detection with 18F FACBC PET/CT: comparison with MR imaging and histopathologic analysis. Radiology 2014; 270: 849-856
  CrossrefPubMedGoogle Scholar
• 72 Van de Wiele C, Dumont F, Dierckx RA et al. Biodistribution and Dosimetry of 99mTc-RP527, a Gastrin-Releasing Peptide (GRP) Agonist for the Visualization of GRP Receptor–Expressing Malignancies. Journal of Nuclear Medicine 2001; 42: 1722-1727
  PubMedGoogle Scholar
• 73 Van de Wiele C, Dumont F, Vanden Broecke R et al. Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study. European journal of nuclear medicine 2000; 27: 1694-1699
  CrossrefPubMedGoogle Scholar
• 74 Vavere AL, Kridel SJ, Wheeler FB et al. 1-11C-acetate as a PET radiopharmaceutical for imaging fatty acid synthase expression in prostate cancer. J Nucl Med 2008; 49: 327-334
  CrossrefPubMedGoogle Scholar
• 75 Weineisen M, Simecek J, Schottelius M et al. Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer. EJNMMI Research 2014; 4: 63
  CrossrefPubMedGoogle Scholar
• 76 Wernicke AG, Edgar MA, Lavi E et al. Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme. Archives of pathology & laboratory medicine 2011; 135: 1486-1489
  CrossrefPubMedGoogle Scholar
• 77 Wieser G, Mansi R, Grosu AL et al. Positron Emission Tomography (PET) Imaging of Prostate Cancer with a Gastrin Releasing Peptide Receptor Antagonist – from Mice to Men. Theranostics 2014; 4: 412-419
  CrossrefPubMedGoogle Scholar
• 78 Wright Jr GL, Haley C, Beckett ML et al. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urologic oncology 1995; 1: 18-28
  CrossrefPubMedGoogle Scholar
• 79 Zechmann CM, Afshar-Oromieh A, Armor T et al. Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging 2014; 41: 1280-1292
  CrossrefPubMedGoogle Scholar
• 80 Zhang AX, Murelli RP, Barinka C et al. A remote arene-binding site on prostate specific membrane antigen revealed by antibody-recruiting small molecules. J Am Chem Soc 2010; 132: 12711-12716
  CrossrefPubMedGoogle Scholar
• 81 Zhang H, Chen J, Waldherr C et al. Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors. Cancer Res 2004; 64: 6707-6715
  CrossrefPubMedGoogle Scholar
• 82 Zhang H, Schuhmacher J, Waser B et al. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours. Eur J Nucl Med Mol Imaging 2007; 34: 1198-1208
  CrossrefPubMedGoogle Scholar
• 83 Zhou D, Lin M, Yasui N et al. Optimization of the preparation of fluorine-18-labeled steroid receptor ligands 16alpha-[18F]fluoroestradiol (FES), [18F]fluoro furanyl norprogesterone (FFNP), and 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT) as radiopharmaceuticals. Journal of labelled compounds & radiopharmaceuticals 2014; 57: 371-377
  CrossrefPubMedGoogle Scholar