Radiotherapy and dosimetry of Cu-64-TETA-Tyr(3)-octreotate in a somatostatin receptor-positive, tumor-bearing rat model

Citation
Js. Lewis et al., Radiotherapy and dosimetry of Cu-64-TETA-Tyr(3)-octreotate in a somatostatin receptor-positive, tumor-bearing rat model, CLIN CANC R, 5(11), 1999, pp. 3608-3616
Citations number
36
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
10780432 → ACNP
Volume
5
Issue
11
Year of publication
1999
Pages
3608 - 3616
Database
ISI
SICI code
1078-0432(199911)5:11<3608:RADOCI>2.0.ZU;2-G
Abstract
Cu-64 [T-1/2= 12.8 h; beta(+) = 0.655 MeV (19%); beta(-) = 0.573 MeV (40%)] has shown promise as a radioisotope for targeted radiotherapy, It has been demonstrated previously that the somatostatin analogue Cu-64-TETA-octreoti de (Cu-64-TETA-OC, where TETA is 1,4,8,11-tetraazacyclotetradecane-N,N',N " ,N'''-tetraacetic acid) significantly inhibited the growth of somatostatin receptor-positive CA20918 rat pancreatic tumors in Lewis rats (C. J. Anders on et al,, J. Nucl. Med., 39: 1944-1951, 1998), In this study, we evaluated the radiotherapeutic efficacy of a new Cu-64-labeled somatostatin analogue , Cu-64-TETA-Tyr(3)-octreotate (Cu-64-TETA-Y3-TATE), in CA20948 tumor-beari ng rats. A single dose of 15 mCi (555 MBq) of Cu-64-TETA-Y3-TATE was shown to be more effective in reducing tumor burden than the same dose of 64Cu-TE TA-OC. In multiple dose experiments, tumor-bearing rats were administered t hree doses of either 10 or 20 mCi (370 or 740 MBq) of Cu-64-TETA-Y3-TATE at 48-h intervals. Rats given 3 x 10 mCi (3 x 370 MBq) showed extended mean s urvival times compared with rats given a single dose; however, no complete regressions occurred. Complete regression of tumors was observed for all ra ts treated with 3 x 20 mCi (3 x 740 MBq), with no palpable tumors for simil ar to 10 days; moreover, the mean survival time of these rats was nearly tw ice that of controls. Toxicity was determined by physical appearance and he matological and enzyme analysis, which revealed no overt toxicity and only transient changes in blood and liver chemistry. Absorbed dose estimates sho wed the dose-limiting organ to be the kidneys. The radiotherapy results, al ong with absorbed dose estimates to target and clearance organs, confirm th at Cu-64-labeled somatostatin analogues warrant continued consideration as agents for targeted radiotherapy.