Comparative dosimetry of copper-64 and yttrium-90-labeled somatostatin analogs in a tumor-bearing rat model

Y-90-DOTA -tyrosine(3)-octreotide (Y-90-DOTA-Y3-OC) is currently being evaluated as a radiotherapy agent for trials in patients with somatostatin-receptor positive cancer. In this study, we compared the estimated absorbed doses to human organs, as well as to a CA20948 rat tumor, of Y-90- and Cu-64-labeled DOTA-Y3-OC and DOTA-Y3-octreotate (DOTA-Y3-TATE). Assuming that the radiopharmaceutical biodistributions are the same in rodents and humans, human absorbed dose estimates were obtained from rat biodistribution data. The absorbed doses of Y-90-DOTA-Y3-TATE were determined from the biodistribution of the Y-88-labeled peptide, with and without co-injection of a therapeutic amount of the Y-90-labeled peptide. Additionally, the absorbed doses of Y-90-DOTA-Y3-TATE were determined from data using two different biodistribution endpoints, 48 h and 168 h. Human absorbed dose estimates were calculated using MIRD methodology assuming that rats and humans have the same biodistribution. The biodistribution of the radiolabeled somatostatin analogs was dependent on the peptide and the radiometal. For 90Y-DOTA-Y3-TATE, the tumor dose was dependent on both the administration of therapeutic Y-90-peptide and the biodistribution endpoint. Our data suggested that, for both radionuclides, the TATE derivatives imparted a higher absorbed dose to the tumor than the OC analogs. Y-90-DOTA-Y3-OC and Cu-64-DOTA-Y3-OC were comparable with respect to their tumor-to-normal tissue dose ratios, while Y-90-DOTA-Y3-TATE appeared to have distinct advantages over Cu-64-DOTA-Y3-TATE.