CYCLIC CHOLECYSTOKININ ANALOGUES EXHIBIT HIGH BLOOD STABILITY AND BINDING AFFINITY WITH CHOLECYSTOKININ RECEPTOR
Eun-Ha Joh, Jae Cheong Lim, Jin Joo Kim, Sang Mu Choi and Sun-Ju Choi
DOI : 10.3844/ojbsci.2014.26.35
OnLine Journal of Biological Sciences
Volume 14, Issue 1
Recently, incidence of Cholecystokinin (CCK) receptor is recognized as a factor that determines the aggressive phenotype of pancreatic cancer. In this study, a novel Cholecystokinin (CCK) analogues; DOTA-Nle-cyclo (Glu-Trp-Met-Asp-Phe-Lys-NH2) (DOTA-cCCK) and DOTA-Nle-cyclo (Glu-Trp-Nle-Asp-Phe-Lys-NH2) (DOTA-[Nle]-cCCK) were synthesized and radiolabeled and the targeting abilities on the CCK receptor were evaluated for new CCK receptor targeting agents searching. Peptides were prepared through a solid phase synthesis method and their purity was over 98%. DOTA is the chelating agent for 68Ga-labelling, which the peptides were radiolabeled with 68Ga by a high radiolabeling yield (>98%). Peptides were stable over 98% by incubation in mouse blood at 37°C for 2 h. A competitive displacement of 125I-CCK8 on the AR42J human pancreatic carcinoma cells revealed that 50% inhibitory concentration value (IC50) were 12.31 nM of DOTA-cCCK and 1.69 nM of DOTA-[Nle]-cCCK. Stable in the blood of both DOTA-cCCK and DOTA-[Nle]-cCCK, but the binding rate with the CCK receptor on AR42J cells, DOTA-[Nle]-cCCK confirmed better than DOTA-cCCK. Therefore, it is concluded that 68Ga-DOTA-[Nle]-cCCK can be potential candidate as a targeting modality for the CCK receptor over-expressing tumors and further studies to evaluate their biological characteristics are needed.
© 2014 Eun-Ha Joh, Jae Cheong Lim, Jin Joo Kim, Sang Mu Choi and Sun-Ju Choi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.