Efficacy of multiple treatment cycles of ¹⁷⁷Lu-DOTA-8-AOC-BBN(7-14)NH₂ in combination with docetaxel in PC-3 human prostate cancer xenografts

Abstract

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Objectives: Targeted radiotherapy (TRT) combined with chemotherapy has shown great promise as a means of treatment for PC-3 human prostate cancer in xenograft mouse models. Previous preclinical therapy studies in our laboratory employing single dose ¹⁷⁷Lu-DOTA-8-AOC-BBN(7-14)NH₂ in combination with Docetaxel (DOC) demonstrated enhanced survival with transient tumor control. The current study implemented multiple treatment cycles of ¹⁷⁷Lu-DOTA-8-AOC-BBN(7-14)NH₂ in combination with DOC in an effort to improve survival and tumor control using the PC-3 human prostate cancer xenograft mouse model. Methods: PC-3 xenografts were prepared using a SCID mouse model with subcutaneous bilateral flank inoculations. DOTA-8-AOC-BBN(7-14)NH₂ was synthesized using standard solid phase peptide synthesis. ¹⁷⁷Lu-DOTA-8-AOC-BBN(7-14)NH₂ was prepared and purified by HPLC prior to i.v. administration. DOC was prepared according to the package insert and diluted with sterile saline. Tumor size, body condition, and body weight were evaluated at least weekly in the following groups: Control, DOC, TRT, and TRT + DOC. Each treatment cycle consisted of weekly DOC (15 mg/kg i.p.) administrations for 5 consecutive weeks and bi-weekly TRT (1.48 GBq/kg) administrations (3 administrations). Results: At 39 days post study initiation, the tumor volume measurements showed 95%, 83%, and 71% tumor suppression for TRT + DOC, DOC, and TRT groups, respectively, as compared to the non-treated controls. The mean survival was 54, 111, 89, and 175 days for the control, DOC, TRT, and TRT + DOC groups, respectively. Conclusions: Mean survival of the TRT + DOC treatment group was increased by approximately 70 days (64%) with three treatment cycles when compared to a single treatment cycle. This data suggests that BB2 receptor targeted radiotherapy used in combination with selective chemotherapeutic agents may prove effective in the treatment of androgen independent prostate cancer.

Research Support (if any): American Cancer Society RSG-99-331-04-CDD, National Cancer Institute DHHS-R01-CA72942