期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 131, 期 3, 页码 209-214出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2016.06.006
关键词
Lutetium-177; Radioisotope; Targeting; Cancer; Radiotherapy
资金
- KAERI Major Project, Development of Radioisotope Production and Application Technology based on Research Reactor [525140-16]
The cholecystokinin (CCK) receptor is known as a receptor that is overexpressed in many human tumors. The present study was designed to investigate the targeting ability of cyclic CCK analogue in AR42J pancreatic cells. The CCK analogues, DOTA-K(glucose)-Gly-Trp-Nle-Asp-Phe (DOTA-glucose-CCK) and DOTA-Nle-cyclo(Glu-Trp-Nle-Asp-Phe-Lys-NH2) (DOTA-[Nle]-cCCK), were synthesized and radiolabeled with Lu-177, and competitive binding was evaluated. The binding appearance of synthesized peptide with AR42J cells was evaluated by confocal microscopy. And bio-distribution was performed in AR42J xenografted mice. Synthesized peptides were prepared by a solid phase synthesis method, and their purity was over 98%. DOTA is the chelating agent for Lu-177-labeling, in which the peptides were radiolabeled with Lu-177 by a high radiolabeling yield. A competitive displacement of I-125-CCK8 on the AR42J cells revealed that the 50% inhibitory concentration value (IC50) was 12.3 nM of DOTA-glucose-CCK and 1.7 nM of DOTA-[Nle]-cCCK. Radio-labeled peptides were accumulated in AR42J tumor in vivo, and % ID/g of the tumor was 0.4 and 0.9 at 2 h p.i. It was concluded that Lu-177-DOTA-[Nle]-cCCK has higher binding affinity than Lu-177-DOTA-glucose-CCK and can be a potential candidate as a targeting modality for a CCK receptor over-expressing tumors. (C) 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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