Radiotherapy and dosimetry of 64Cu-TETA-Tyr3-octreotate in a somatostatin receptor-positive, tumor-bearing rat model

Jason S. Lewis, Michael R. Lewis, P. Duffy Cutler, Ananth Srinivasan, Michelle A. Schmidt, Sally W. Schwarz, Margaret M. Morris, J. Philip Miller, Carolyn J. Anderson

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101 Scopus citations

Abstract

64Cu [T( 1/2 ) = 12.8 h; β+ = 0.655 MeV (19%); β- = 0.573 MeV (40%)] has shown promise as a radioisotope for targeted radiotherapy. It has been demonstrated previously that the somatostatin analogue 64Cu-TETA-octreotide (64Cu-TETA-OC, where TETA is 1,4,8,11-tetraazacyclotetradecane-N,N',N,N'- tetraacetic acid) significantly inhibited the growth of somatostatin receptor-positive CA20948 rat pancreatic tumors in Lewis rats (C. J. Anderson et al., J. Nucl. Med., 39: 1944-1951, 1998). In this study, we evaluated the radiotherapeutic efficacy of a new 64Cu-labeled somatostatin analogue, 64Cu-TETA-Tyr3-octreotate (64CuTETA-Y3-TATE), in CA20948 tumor-bearing rats. A single dose of 15 mCi (555 MBq) of 64Cu-TETA-Y3-TATE was shown to be more effective in reducing tumor burden than the same dose of 64Cu-TETA- OC. In multiple dose experiments, tumor-bearing rats were administered three doses of either 10 or 20 mCi (370 or 740 MBq) of 64Cu-TETA-Y3TATE at 48-h intervals. Rats given 3 x 10 mCi (3 x 370 MBq) showed extended mean survival times compared with rats given a single dose; however, no complete regressions occurred. Complete regression of tumors was observed for all rats treated with 3 x 20 mCi (3 x 740 MBq), with no palpable tumors for ~10 days; moreover, the mean survival time of these rats was nearly twice that of controls. Toxicity was determined by physical appearance and hematological and enzyme analysis, which revealed no overt toxicity and only transient changes in blood and liver chemistry. Absorbed dose estimates showed the dose-limiting organ to be the kidneys. The radiotherapy results, along with absorbed dose estimates to target and clearance organs, confirm that 64Cu- labeled somatostatin analogues warrant continued consideration as agents for targeted radiotherapy.

Original languageEnglish
Pages (from-to)3608-3616
Number of pages9
JournalClinical Cancer Research
Volume5
Issue number11
StatePublished - Nov 1999

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