Evaluation of Lu-177 RM2 as a targeted radiopharmaceutical in a PC-3 xenograft model of androgen-independent prostate cancer.

Abstract

e13522 Background: Prostate cancer is the most common cancer in American men (after nonmelanoma skin cancers). In 2010 more than 200,000 cases were diagnosed and more than 30,000 men died of prostate cancer. One in six men will be diagnosed with prostate cancer during his lifetime and one in thirty six men will die of prostate cancer. Human prostate cancer has been shown to widely express the bombesin receptor (BB2R). Lutetium-177 (177 Lu) radiolabeled BB2r agonist analogs are currently being investigated preclinically for their utility as targeted radiation therapy agents. (Maddalena, J Nucl Med, 50:2017, 2009 and Johnson, Can Biother & Radiopharm, 21(2):155, 2006) Recently, Maecke and co-workers identified a high affinity BB2r antagonist (Ga-68 and In-111-RM2) for potential use as a PET/SPECT diagnostic imaging agent. (Mansi, Clin Can Res, 15(16):5240, 2009 and Mansi, Eur J Nucl Med Mol Imaging, May 2010) The purpose of this work was to investigate the biodistribution of Lu-177-RM2 for potential as a radiotherapeutic agent using a PC-3 xenografted SCID mouse model. Methods: Male SCID mice were inoculated subcutaneously with 5 million PC-3 cells/site in 100uL. At 4 weeks post-inoculation, pharmacokinetic studies of 177Lu-VA RM2 were conducted at 1, 4, 24, 48, 72, and 96 hours post-injection. Micro-SPECT/CT imaging studies were done at 24, 48, 72, and 96 hrs. Results: See table; shown in %ID/g. Conclusions: Our study demonstrates that Lu-177-RM2 shows promising pharmacokinetic properties with high affinity for the BB2 receptor and excellent tumor to blood and tumor to organ ratios. The prostate tumor uptake of Lu-177-RM2 is equal or greater than any previously identified BB2r targeting radiotherapeutic agent. Lu-177-RM2 exhibits rapid washout from the pancreas and other non-target organs making it an ideal candidate for tumor targeted therapy research. 1 HR 4 HRS 24 HRS 48 HRS 72 HRS 96 HRS Blood 0.36 +/- 0.15 0.02 +/- 0.01 0.00 +/- 0.00 0.00 +/- 0.00 0.00 +/- 0.00 0.00 +/- 0.00 Pancreas 17.53 +/- 1.97 1.59 +/- 0.7 0.26 +/- 0.03 0.18 +/- 0.04 0.19 +/- 0.03 0.03 +/- 0.00 Tumor 9.25 +/- 3.35 11.46 +/- 5.38 5.56 +/- 1.59 5.28 +/- 1.42 4.03 +/- 0.92 3.14 +/- 0.33