Research Information System
Journal of Medicinal Chemistry, vol.52, no.15, pp.4786-4793, 2009 (SCI-Expanded)
Two cyclized minigastrin analogues for gastrin receptor scintigraphy were synthesized and derivatized with HYNIC at the N-terminus for labeling with Tc-99m. Radiolabeling efficiency, stability, cell internalization, and receptor binding on CCK-2 receptor expressing AR42J cells were studied and the biodistribution evaluated in tumor bearing nude mice, including NanoSPECT/CT imaging. Metabolites in urine, liver, and kidneys were analyzed by radio-HPLC. Radiolabeled cyclic MG showed high stability in vitro and receptor mediated uptake in AR42J cells. In the animal tumor model, fast renal clearance and low nonspecific uptake in most organs were observed. A tumor uptake > 3% was calculated ex vivo 1 h p.i. for both Tc-99m-EDDA-HYNIC-cyclo-MG1 and Tc-99m-EDDA-HYNIC-cyclo-MG2. In an imaging study with Tc-99m-EDDA-HYNIC-cyclo-MG1, the tumor was clearly visualized. The metabolite analysis indicated rapid enzymatic degradation in vivo.