Cyclic Minigastrin Analogues for Gastrin Receptor Scintigraphy with Technetium-99m: Preclinical Evaluation

Two cyclized minigastrin analogues for gastrin receptor scintigraphy were synthesized and derivatized with HYNIC at the N-terminus for labeling with 99mTc. Radiolabeling efficiency, stability, cell internalization, and receptor binding on CCK-2 receptor expressing AR42J cells were studied and the bi...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2009-08, Vol.52 (15), p.4786-4793
Main Authors: von Guggenberg, Elisabeth, Sallegger, Werner, Helbok, Anna, Ocak, Meltem, King, Robert, Mather, Stephen J, Decristoforo, Clemens
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Biological and medical sciences
Contrast media. Radiopharmaceuticals
Drug Evaluation, Preclinical
Female
Gastrins - chemical synthesis
Gastrins - pharmacokinetics
Isotope Labeling
Medical sciences
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Neoplasms, Experimental - metabolism
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Radiopharmaceuticals - chemical synthesis
Receptor, Cholecystokinin B - analysis
Technetium
Tissue Distribution
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Two cyclized minigastrin analogues for gastrin receptor scintigraphy were synthesized and derivatized with HYNIC at the N-terminus for labeling with 99mTc. 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 99mTc-EDDA-HYNIC-cyclo-MG1 and 99mTc-EDDA-HYNIC-cyclo-MG2. In an imaging study with 99mTc-EDDA-HYNIC-cyclo-MG1, the tumor was clearly visualized. The metabolite analysis indicated rapid enzymatic degradation in vivo.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm900400w