Abstract 5347: Preliminary evaluation of BB2r TAT using 212Pb-RM2 in a PC3 human prostate cancer xenograft model

Abstract

Abstract Introduction: Targeted alpha therapy (TAT) employing radiolabeled receptor targeted peptides holds the potential to be clinically effective for the treatment of advanced prostate cancer. We are evaluating the use of the TAT agent, Pb-212-RM2, for targeting the BB2r receptor shown to be expressed in prostate cancer. The current study is the initial therapeutic efficacy evaluation of Pb-212-RM2 TAT administered as a single bolus injection using the androgen independent/insensitive PC3 human prostate cancer xenograft model. Methods: SCID mice (4-5 weeks of age) were injected subcutaneously with 5 million cultured PC3 cells in both rear flanks as a suspension in RPMI 1640 media. The RM2 peptide was obtained commercially. Pb-212 was eluted from a Ra-224/Pb-212 generator and synthesis of Pb-212-RM2 performed using an Eckert & Ziegler PharmTracer. QC was conducted using HPLC. PC3 xenografted SCID mice were administered a single intravenous bolus of saline (NTC), 0.3ug Pb-RM2 (Cold RM2), 50uCi or 100uCi of 212Pb-RM2 in approximately 100uL via the tail vein. Weekly caliper tumor measurements, complete blood counts (CBC), body weight (BW), and body condition score (BCS) were taken predose and up to 17 weeks post injection (pi). Results: At 18 days pi, tumor regression was observed in the 100uCi group with a maximum percent change of -49.3%, while the 50uCi dose group revealed slight tumor growth (+17.2%). As expected, the NTC and Cold RM2 groups demonstrated rapid tumor growth (+325.3% and +304.5% change, respectively). By day 40 pi, tumor regrowth was observed in the 100uCi group (+91.6% change from predose with a +221.1% change by day 47). Body weights of the NTC, Cold RM2, 50uCi and 100uCi groups at 7 days pi were 101.5%, 101.5%, 98.5%, and 95.4%, respectively. Platelet count comparisons between the NTC group and the 50uCi (P=0.0544) and 100uCi (P=0.0624) groups were comparable. Conclusions: Both Pb-212-RM2 TAT treatment groups (50uCi and 100uCi) demonstrated initial tumor control for 4-5 weeks post treatment. While tumor growth suppression was evident in only the 100uCi dose group, this suppression was transient with tumor volume increasing steadily beginning at 32 days pi. As expected, the non-radioactive Pb-RM2 had no effect on tumor growth. Body weights for all dose groups remained >95% of predose weights until disease progression required subject removal from the study. These results warrant further evaluation of multi-dose administration of Pb-212-RM2 with and without standard of care chemotherapy to evaluate optimal tumor control properties of BB2r TAT. This work was supported by USVA IK6BX004856, USVA IO1BX001699, and NCI RO1CA222293. Citation Format: Tammy L. Rold, Elisabeth A. Devanny, Nkemakonam C. Okoye, Thomas P. Quinn, Timothy J. Hoffman. Preliminary evaluation of BB2r TAT using 212Pb-RM2 in a PC3 human prostate cancer xenograft model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5347.