Abstract 2682: Imaging prostate cancer in an orthotopic prostate model using a 68Ga-Bombesin (BB2r) radiopharmaceutical.

Introduction: There continues to remain a significant need to develop molecular imaging agents for the diagnosis and staging of prostate cancer. The association of the bombesin receptor subtype 2 (BB2r) and prostate cancer is well known and several groups including our own have developed unique radiopharmaceutical targeting strategies for the delivery of BB2r agonists and antagonists. Earlier work from our group utilizing BB2r agonists and antagonists labeled with 99m Tc and 111 In demonstrated selective targeting of simple flank xenograft models of prostate cancer. We are now presenting a preclinical evaluation of 68 Ga-BB2r PET imaging using an orthotopic prostate SCID mouse model. Methods: The BB2r antagonist, DOTA-4-Amino-Carboxymethyl-Piperidine-DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, (Eur J Nucl Med Mol Imaging 38(1):97, 2011) was synthesized commercially. 68 Ga was obtained from a commercially available Ge-68/Ga-68 generator. The peptide (40ug) was radiolabeled with 10-20mCi (270-740MBq) of 68 Ga using an automated radiosynthesis system. Reverse phase HPLC (C-18) was employed for quality control analysis using a combination of radiometric and UV analysis. Orthotopic prostate xenografted male SCID mice were administered ∼0.3mCi (11.1 MBq) of 68 Ga labeled peptide and combined PET/CT imaging was performed 4 hours following injection. Each mouse received 100uL of Visipaque® before imaging commenced. Concurrent 7 T MRI data was obtained for anatomic verification of prostate tumor involvement. Pathologic confirmation of tumor involvement within the prostate bed was obtained. Results: The 68 Ga BB2r antagonists could be readily prepared in high radiochemical yield and purity as verified by HPLC. Orthotopic prostate tumor xenografts were clearly visualized using PET/CT imaging. The predominant renal clearance of the tracer presented challenges in differentiating active tumor involvement within the prostate bed from bladder contents. These challenges could be partially addressed by employing concurrent CT contrast agent administration as an aid in accurately defining bladder contents and balder wall delineation. Conclusions: These results demonstrate that 68 Ga BB2r antagonist PET/CT imaging holds the potential to accurately differentiate BB2r positive prostate tumor growth within the prostate bed as a potential screening and diagnostic tool. Citation Format: Kelsey Richmond, Tammy Rold, Ashley Szczodroski, Lixin Ma, Quanyu Cai, Timothy Hoffman. Imaging prostate cancer in an orthotopic prostate model using a 68 Ga-Bombesin (BB2r) radiopharmaceutical. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2682. doi:10.1158/1538-7445.AM2013-2682