Antiangiogenic therapy with somatostatin receptor-mediated in situ radiation

Tumor growth and the development of metastases require an angiogenic respon se. Angiogenic vessels uniquely express somatostatin subtype 2 (sst 2) rece ptors that can transport somatostatin or its analogs into the cell. We hypo thesized that radiolabeled somatostatin analogs could inhibit the angiogeni c response by selectively destroying proliferating endothelial cells. We ev aluated the antiangiogenic effects of In-111-pentetreotide, an sst 2-prefer ring somatostatin analog in a human vessel model. Disks of human placental vein were embedded in fibrin gels in culture and observed for angiogenic sp routing for 14 days. Vein disks were treated with In-111-pentetreotide (1.5 , 15, and 150 mu Ci/mL) on the day of implantation. Control groups included disks treated with nutrient medium alone, with In-111-chloride, and with u nlabeled pentetreotide. The percentage of wells that initiated an angiogeni c response and the overall length and density of neovessel sprouts were ass essed on Day 14. In-111-pentetreotide treatment did not completely block in itiation of the angiogenic response but significantly decreased the growth of neovessels after initiation. Both the receptor-specific Auger electron-i nduced and nonspecific gamma radiation-mediated effects contributed to the angiotoxicity.