title: An assessment tumor targeting ability of (177)Lu labeled cyclic CCK analogue peptide by binding with cholecystokinin receptor.
abstract: 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 (177)Lu, 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 (177)Lu-labeling, in which the peptides were radiolabeled with (177)Lu by a high radiolabeling yield. A competitive displacement of (125)I-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 (177)Lu-DOTA-[Nle]-cCCK has higher binding affinity than (177)Lu-DOTA-glucose-CCK and can be a potential candidate as a targeting modality for a CCK receptor over-expressing tumors.
authors.affiliation: RI Research Division, Research Reactor Utilization Department, Korea Atomic Energy Research Institute (KAERI), Daejeon 305-353, Republic of Korea. Electronic address: choeh36@kaeri.re.kr.
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Cho
authors.affiliation: RI Research Division, Research Reactor Utilization Department, Korea Atomic Energy Research Institute (KAERI), Daejeon 305-353, Republic of Korea.
authors.forename: Jae Cheong
authors.initials: JC
authors.lastname: Lim
authors.affiliation: RI Research Division, Research Reactor Utilization Department, Korea Atomic Energy Research Institute (KAERI), Daejeon 305-353, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: RI Research Division, Research Reactor Utilization Department, Korea Atomic Energy Research Institute (KAERI), Daejeon 305-353, Republic of Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Jung
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002766:Cholecystokinin / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D008187:Lutetium / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000473:pathology; D010456:Peptides, Cyclic / Q000378:metabolism*; D011485:Protein Binding; D011868:Radioisotopes / Q000378:metabolism*; D011869:Radioligand Assay; D011949:Receptors, Cholecystokinin / Q000378:metabolism*
chemical_list: D010456:Peptides, Cyclic; D011868:Radioisotopes; D011949:Receptors, Cholecystokinin; D008187:Lutetium; D002766:Cholecystokinin
keywords: Cancer; Lutetium-177; Radioisotope; Radiotherapy; Targeting