Radiotherapy, toxicity and dosimetry of copper-64-TETA-octreotide in tumor-bearing rats.
The efficacy of 64Cu [T1/2 = 12.7 hr; beta+ (0.655 MeV; 19%); beta- (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.


CONCLUSIONS
Copper-64-TETA-octreotide is a promising radiopharmaceutical for targeted radiotherapy of somatostatin receptor-positive tumors.
Anderson
C J
CJ
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Jones
L A
LA
Bass
L A
LA
Sherman
E L
EL
McCarthy
D W
DW
Cutler
P D
PD
Lanahan
M V
MV
Cristel
M E
ME
Lewis
J S
JS
Schwarz
S W
SW
D000818:Animals; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D006801:Humans; D007958:Leukocyte Count / Q000528:radiation effects; D008297:Male; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D011879:Radiotherapy Dosage; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution
D003301:Copper Radioisotopes; D019275:Radiopharmaceuticals; C097225:octreotide, TETA-Phe(1)-; D015282:Octreotide