Evaluation of combined (177)Lu-DOTA-8-AOC-BBN (7-14)NH(2) GRP receptor-targeted radiotherapy and chemotherapy in PC-3 human prostate tumor cell xenografted SCID mice

The focus of this study was to evaluate the therapeutic benefit of combined gastrin-releasing peptide (GRP) receptor-targeted radiotherapy (TRT) with chemotherapy, using the PC-3 xenograft severe combined immunodeficiency (SCID) mouse model. (177)Lu-DOTA-8-AOC-BBN(7-14)NH(2) is a radiotherapeutic peptide that specifically targets the gastrin-releasing peptide receptor overexpressed on primary and metastatic prostate cancer. The chemotherapeutic agents, docetaxel and estramustine, were administered as single agents or in combination with the receptor-targeted radiotherapeutic agent. Combination receptor TRT/chemotherapy studies were begun 21 days postxenografting and were conducted as multiple-dose trials. The GRP receptor TRT agent was administered every 14 days, and single and combination chemotherapy dose regimens were given weekly. Tumor size, body weight, and body condition score were evaluated twice-weekly and a hematology profile once-weekly. Therapy study tumor volumes were evaluated by way of a repeated measures analysis of variance (ANOVA). Tumor volume measurements at 12 days postdose administration demonstrated a statistically significant (two-tailed P-value <0.05) tumor growth suppression in all experimental groups receiving GRP receptor-targeted radiotherapy, when compared to the control group. The two combined GRP receptor TRT/chemotherapy treatment groups demonstrated the greatest tumor growth suppression of all treatment groups. In comparing the two combined GRP receptor TRT/chemotherapy groups to the GRP receptor TRT alone group, a statistically significant difference was demonstrated for the combined groups by day 30, postdose administration. These data demonstrate that GRP receptor-targeted radiation therapy, using (177)Lu-DOTA-8-AOC-BBN(7-14)NH(2), used either alone or in combination with conventional chemotherapy, can suppress the growth of androgen- independent prostate cancer (AIPC).