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

Carolyn J. Anderson, Lynne A. Jones, Laura A. Bass, Elizabeth L.C. Sherman, Deborah W. McCarthy, P. Duffy Cutler, Margaret V. Lanahan, Michael E. Cristel, Jason S. Lewis, Sally W. Schwarz

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1944-1951
Number of pages8
JournalJournal of Nuclear Medicine
Volume39
Issue number11
StatePublished - Nov 1998

Keywords

  • Copper-64
  • Dosimetry
  • Receptor binding
  • Somatostatin analog
  • Targeted radiotherapy

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