Combination radionuclide therapy using 177Lu- and 90Y-labeled somatostatin analogs.
Peptide receptor-targeted radionuclide therapy of somatostatin receptor-expressing tumors is a promising application of radiolabeled somatostatin analogs. Suitable radionuclides are (90)Y, a pure, high-energy beta-emitter (2.27 MeV), and (177)Lu, a medium-energy beta-emitter (0.5 MeV) with a low-abundance gamma.


METHODS
Lewis rats, each bearing both a small (approximately 0.5 cm(2)) and a large (7-9 cm(2)) somatostatin receptor-positive rat pancreatic CA20948 tumor in their flanks, were used. We investigated the radiotherapeutic effects of [(90)Y-tetraazacyclododecanetetraacetic acid (DOTA),Tyr(3)]octreotide, [(90)Y-DOTA,Tyr(3)]octreotate, [(177)Lu-DOTA,Tyr(3)]octreotate, and the combination of (90)Y- and (177)Lu-labeled analogs at the same tumor radiation dose (60 Gy).


RESULTS
Radiotherapeutic effects of the (90)Y- and (177)Lu-labeled analogs were found in the rat tumor model. In these animals bearing tumors of different sizes, the antitumor effects of the combination of 50% (177)Lu- plus 50% (90)Y-analogs were superior to those in animals treated with either (90)Y- or (177)Lu- analog alone. In smaller tumors, the (90)Y radiation energy was not completely absorbed in the tumor, whereas in larger tumors the increased number of clonogenic tumor cells at the fixed level of absorbed dose may account for the failure of (177)Lu alone to go completely into remission.


CONCLUSIONS
This study shows the superior antitumor effects of the combination of (177)Lu- and (90)Y-somatostatin analogs when compared with either (90)Y- or (177)Lu-analog alone in animals bearing tumors of various sizes.
de Jong
Marion
M
Department of Nuclear Medicine, Erasmus Medical College, Rotterdam, The Netherlands. m.hendricks-dejong@erasmusmc.nl
Breeman
Wout A P
WA
Valkema
Roelf
R
Bernard
Bert F
BF
Krenning
Eric P
EP
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D045744:Cell Line, Tumor; D006801:Humans; D008187:Lutetium / Q000008:administration & dosage*; D008297:Male; D015282:Octreotide / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D009942:Organometallic Compounds / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D011868:Radioisotopes / Q000008:administration & dosage*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016019:Survival Analysis; D016896:Treatment Outcome; D015019:Yttrium / Q000008:administration & dosage*
D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013004:Somatostatin; D015019:Yttrium; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; D015282:Octreotide; C106246:Edotreotide