Preclinical evaluation of 177Lu-BBR2 antagonist radiothearpy of prostate cancer
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Castration resistant prostate cancer (CRPC) is the second most common cause of cancer death in the United States. Current treatment protocols offer only a few months of prolonged survival. Bombesin receptor subtype two (BBr2) has been shown to be overexpressed in prostate cancer. The objective of this project is to evaluate the efficacy of a 177Lu-BBr2 agonist verses a 177Lu-BBr2 antagonist targeted radiotherapy in a preclinical xenografted mouse model of CRPC. PC-3, a prostate cancer cell line known to express BBr2, xenografted male SCID mice were used as a model of CRPC. Commercially synthesized BBr2 agonist (DOTA-8-AOC-BBN[7-14]NH2) and antagonist (DOTA-RM2) were labeled with 177Lu. Mice were randomized into 8 groups including control, chemotherapy (docetaxel; 8 mg/kg IP weekly), radiotherapy (either 177Lu-BB2r agonist or 177Lu-BB2r antagonist peptide IV; administered weekly), and combination therapy. Treatment was delivered for six consecutive weeks. Tumor volume, body condition score, and weight were measured weekly to assess efficacy. Single agent 177Lu-BB2r antagonist resulted in superior tumor volume control (p<0.0001) and survival (p<0.0001) when compared to the 177Lu-BB2r agonist administered in combination with chemotherapy. No toxicity was observed in mice receiving 177Lu-BB2r antagonist alone.
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