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

Jason S. Lewis, Richard Laforest, Michael R. Lewis, Carolyn J. Anderson

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

90Y-DOTA-tyrosine3-octreotide (90Y-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 90Y-and 64 Cu-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 90Y-DOTA-Y3-TATE were determined from the biodistribution of the 88Y-labeled peptide with and without co-injection of a therapeutic amount of the 90Y-labeled peptide. Additionally the absorbed doses of 90Y-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 90Y-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. 90Y-DOTA-Y3-OC and 64Cu-DOTA-Y3-OC were comparable with respect to their tumor-to-normal tissue dose ratios while 90Y-DOTA-Y3-TATE appeared to have distinct advantages over 64Cu-DOTA-Y3-TATE.

Original languageEnglish
Pages (from-to)593-604
Number of pages12
JournalCancer Biotherapy and Radiopharmaceuticals
Volume15
Issue number6
DOIs
StatePublished - 2000

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