An assessment tumor targeting ability of 177Lu labeled cyclic CCK analogue peptide by binding with cholecystokinin receptor

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 177lu,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 177lu-labeling,in which the peptides were radiolabeled with 177lu by a high radiolabeling yield. a competitive displacement of 125i-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 177lu-dota-[nle]-ccck has higher binding affinity than 177lu-dota-glucose-cck and can be a potential candidate as a targeting modality for a cck receptor over-expressing tumors. © 2016 the authors