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
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.