Biodistribution and Dosimetry of ¹⁷⁷Lu-Labeled [DOTA⁰,Tyr³]Octreotate in Male Nude Mice with Human Small Cell Lung Cancer

Abstract

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.

Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2

“…As a consequence of the lower GOT2 uptake the mean absorbed dose to the tumor from 177 Lu-octreotate was much lower for GOT2 tumors (0.011 Gy/MBq) than for GOT1 tumors (1.6-4.0 Gy/MBq) (17,48) and H69 tumors (0.29 Gy/ MBq) (18). It should be noted that successful therapy has been achieved both in the GOT1 and H69 mouse models (17,19).…”

“…When comparing the biodistribution data of 177 Lu-octreotate with corresponding data in animal models with other types of SSTR-expressing tumors differences between the models were found (Table III). The 177 Lu activity concentration in GOT2 was much lower than that of the midgut carcinoid GOT1 and small cell lung cancer (SCLC) H69 (about 45 and 10 times lower, respectively) based on studies performed in our laboratory (17,18). The reason is the very high SSTR expression in these cell lines and low SSTR expression in GOT2 (39).…”

“…The tumor/normal-tissue activity concentration ratio was highest for blood (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), and muscle vs. all other tissues (Table II). The lowest tumor/normal-tissue value was Table I.…”

“…Numerous studies on radiolabeled octreotide, or octreotate, have been made on nude mice xenografted with GOT1 (14)(15)(16)(17) or NCI-H69 (18)(19)(20)(21). Studies using radioiodinated meta-iodobenzylguanidine (MIBG) have been performed in vitro or on nude mice xenografted with BON tumors (22,23).…”

177Hf as a Competitor in the Synthesis of 177Lu-DOTAtate

“…These radiopharmaceuticals have been used for diagnosis, but mainly for therapeutic use [3][4][5] in neuroendocrine tumors. The 177 Lu is prepared by bombarding a target of enriched 176 Lu with neutrons.…”