Abstract

The iodination of CCK-10 and coupling with PEG 10kDa is described along with evaluation of their food intake reducing effects and in vitro stability. Labeling was performed by electrophilic substitution with both [127I] and [123I] iodide, using iodo-beads® as the oxidant. The reaction conditions were optimised. HPLC was used to follow reaction progression and for purification of the labeled compounds. The synthesized compounds were characterized by MALDI-TOF MS and 1H NMR spectroscopy. Radiochemical yields were 40 ± 3% for [123I]CCK-10; the conjugation with PEG 10kDa was quantitative. A specific activity of 2438 GBq/mmol was obtained. Plasma stability studies with PEG10kDa-[123I]- CCK-10 showed a de-iodination half-life of 27 hours. Food intake experiments in rats with PEG10kDa-[127I]-CCK-10 showed after a single bolus intra-peritoneal injection a food intake reduction during 8 hours equivalent with the results obtained for PEG10kDa-CCK-10 and with PEG10kDa-CCK-9. The pharmacological results obtained indicate that neither the introduction of an extra tyrosine in CCK-9 nor the introduction of a iodine label in tyrosine affects the prolonged food reduction activity of the CCK conjugate. The suitability of PEG10kDa [123I]-CCK-10 as an agent for mapping CCK receptors and pharmacokinetic studies has been shown.

Keywords: Cholecystokinin, CCK-10, PEGylation, PEG10kDa-CCK-10, [, I]-labeled CCK-10, I]-labeled PEG10kDa-CCK-10, food intake, satiety