A standardized study to compare prostate cancer targeting efficacy of five radiolabeled bombesin analogues

• Published in: European journal of nuclear medicine and molecular imaging 2010-07, Vol.37 (7), p.1386
• Main Authors: Schroeder, Rogier P, J, Müller, Cristina, Reneman, Suzanne, Melis, Marleen L, Breeman, Wout A, P, de Blois, Erik, Bangma, Chris H, Krenning, Eric P, van Weerden, Wytske M, de Jong, Marion
• Format: Article
• Language: English
• Subjects: Comparative studies; Prostate cancer; Radioisotopes; Tomography
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-010-1388-2

Prostate-specific antigen (PSA)-based screening for prostate cancer (PC) has dramatically increased early diagnosis. Current imaging techniques are not optimal to stage early PC adequately. A promising alternative to PC imaging is peptide-based scintigraphy using radiolabeled bombesin (BN) analogues that bind to gastrin-releasing peptide receptors (GRPR) being overexpressed in PC. When labeled to appropriate radionuclides BN targeting of GRPRs may also provide applications for peptide radionuclide receptor therapy (PRRT). Assessment studies under identical experimental conditions allowing a reliable comparison of the potential of such analogues are lacking. This study was performed to evaluate and directly compare five promising radiolabeled BN analogues for their targeting efficacy for PC under standardized conditions. The BN agonists [^sup 111^In]DOTA-PESIN, [^sup 111^In]AMBA, [^sup 111^In]MP2346 and [^sup 111^In]MP2653 and one antagonist [^sup 99m^Tc]Demobesin-1 were evaluated in GRPR-overexpressing human PC-3 tumor-bearing mice to determine peptide stability in vivo, biodistribution and GRPR targeting potential by animal SPECT/CT imaging and ex vivo autoradiography. HPLC analysis of blood showed intact Demobesin-1 at 5 and 15 min after injection (64.1±1.6% and 41.0±01%, respectively) being much less for the other compounds. AMBA, the second most stable analogue, showed 36.1±2.7% and 9.8±1.1% intact peptide after 5 and 15 min. PC-3 tumor uptake at 1 h was comparable for Demobesin-1, AMBA, PESIN and MP2346 (3.0±0.4, 2.7±0.5, 2.3±0.5 and 2.1±0.9%ID/g, respectively), but very low for MP2653 (0.9±0.2%ID/g). In addition, MP2346 showed undesirably high uptake in the kidneys (7.9±1.9%ID/g) being significantly less for the other analogues. AMBA, MP2346 and PESIN revealed favorable increases in tumor to blood ratios over time while changes in tumor to kidney and pancreas ratios for Demobesin-1 from 1 to 24 h after injection were significantly better than for the other analogues. All analogues visualized PC-3 tumors by SPECT/CT and autoradiography. In the present study the BN antagonist Demobesin-1 was the best performing analogue showing superior in vivo stability, highest tumor uptake and retention while pancreatic and renal clearance were rapid. PESIN and AMBA were the best GRP agonists with sufficient in vivo stabilities as well as high tumor uptake and retention. Based on these results all three analogues deserve further evaluation for clinical use in PC pat