Cyclic minigastrin analogues for gastrin receptor scintigraphy with technetium-99m: Preclinical evaluation

von Guggenberg E., Sallegger W., Helbok A., Ocak M. , King R., Mather S. J. , ...More

Journal of Medicinal Chemistry, vol.52, no.15, pp.4786-4793, 2009 (Journal Indexed in SCI Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 52 Issue: 15
  • Publication Date: 2009
  • Doi Number: 10.1021/jm900400w
  • Title of Journal : Journal of Medicinal Chemistry
  • Page Numbers: pp.4786-4793


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.