Radiotherapy, toxicity and dosimetry of copper-64-TETA-octreotide in tumor-bearing rats

The efficacy of ⁶⁴Cu [T( 1/2 ) = 12.7 hr; β⁺ (0.655 MeV; 19%); β^- (0.573 MeV; 40%)] as a radioisotope for radiotherapy has been recently established. Here we demonstrate that ⁶⁴Cu-1,4,8,11- tetraazacyclotetradecane-N,N',N',N''-tetraacetic acid (TETA)-octreotide, a somatostatin receptor ligand, inhibits the growth of CA20948 rat pancreatic tumors in Lewis rats at doses that cause minimal toxicity. Methods: Tumor- bearing rats were administered a single 15 mCi (555 MBq) dose, a fractionated dose of 15 mCi given in 2-3 doses over 2-8 days, or control agents of buffer, unlabeled octreotide or ⁶⁴Cu-labeled TETA. In certain experiments, blood was removed at times from 4-23 days post-treatment, and a complete blood count along with blood chemistry analyses were obtained. Results: Tumor- growth inhibition was significantly greater in rats injected with a single 15 mCi dose than in rats injected with control agents (p < 0.05). Dose fractionation in two doses, either 1 or 2 days apart, induced significantly increased tumor-growth inhibition compared with rats given a single dose (p < 0.05). The only toxicity observed in treated rats was a decrease in the white blood cell count. This drop was more pronounced in rats treated with a single dose compared with those treated with a fractionated dose. Human absorbed doses of ⁶⁴Cu-TETA-octreotide to normal organs were estimated from biodistribution data in Lewis rats, and these data indicate that radiotherapy with ⁶⁴Cu-TETA-octreotide in humans would be feasible. Conclusion: Copper- 64-TETA-octreotide is a promising radiopharmaceutical for targeted radiotherapy of somatostatin receptor-positive tumors.