Biodistribution and dosimetry of 177Lu-labeled [DOTA0,Tyr3]octreotate in male nude mice with human small cell lung cancer.
In this study the biodistribution of a somatostatin analogue, (177)Lu-[DOTA(0),Tyr(3)]octreotate, was investigated in an animal model, as a possible therapeutic radiopharmaceutical.


METHODS
(177)Lu-[DOTA(0),Tyr(3)]octreotate was injected i.v. into nude mice bearing somatostatin receptor-positive tumors of the human small cell lung cancer (SCLC) cell line NCI-H69. In addition, nontumor bearing mice were injected i.v. with (177)LuCl(3). The activity concentration in tumor and normal tissues was measured and dosimetric estimations for tumor tissue were made.


RESULTS
The tumor had higher activity concentration of (177)Lu-[DOTA(0),Tyr(3)]octreotate compared to all measured normal tissues at all time points. The activity concentration in the tumor tissue was 3.7 %IA/g, 2.1 %IA/g, and 1.2 %IA/g after 24 h, 3 days and 7 days, respectively. The mean absorbed dose to a 1 g tumor was 0.3 Gy/MBq. The highest activity concentration of (177)LuCl(3) was observed in the bone marrow and increased with time.


CONCLUSIONS
This study shows that (177)Lu-labeled [DOTA(0),Tyr(3)]octreotate has therapeutic potential for SCLC. The study also points out the importance of optimal labeling efficiency since the high bone marrow uptake of free lutetium ions can be controlled by a high peptide-bound fraction.
D000465:Algorithms; D000818:Animals; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor / Q000378:metabolism; D006801:Humans; D008187:Lutetium / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000031:analogs & derivatives; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011868:Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D011878:Radiotherapy; D011879:Radiotherapy Dosage; D013004:Somatostatin / Q000031:analogs & derivatives; D013997:Time Factors; D014018:Tissue Distribution
D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013004:Somatostatin; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; D015282:Octreotide