99mTc-HYNIC-Gastrin Peptides: Assisted Coordination of 99mTc by Amino Acid Side Chains Results in Improved Performance Both In Vitro and In Vivo

The aim of this study was to determine the effects of assisted coor-dination by amino acids such as histidine and glutamic acid on the function of 99mTc-labeled gastrin peptide–hydrazinonicotinamide (HYNIC) conjugates and their ability to target cholecystokinin-R in small-animal models. Methods: Three peptide–HYNIC conjugates containing the-AYGWMDF-NH2 C-terminal sequence and com-binations of histidine, glutamic acid, and glycine were synthesized, radiolabeledwith 99mTc/99Tcusingeither tricineorethylenediamine-diacetic acid as a coligand, and analyzed by the high-performance liquid chromatography and liquid chromatography–mass spectro-metric techniques. Stability, receptor binding, and internalization and in vivo targeting in AR42J-bearing mice were assessed. Re-sults: When radiolabeling was performed using tricine as a coli-gand, the insertion of a histidine residue near the HYNIC residue resulted in the displacement of one molecule of tricine from the co