title: Distribution, elimination, and renal handling of (99m)technetium-Demogastrin 1.
abstract: Radiolabeled cholecystokinin/gastrin (CCK) receptor-targeting peptides are promising compounds for radiodiagnosis and radiotherapy of certain malignancies. This study evaluated the pharmacokinetic profile of a CCK-2 receptor-specific peptide, Demogastrin 1, labeled with technetium-99m ((99m)Tc-Demogastrin 1), in rats. To investigate the fate of (99m)Tc-Demogastrin 1 in the rat, biodistribution and elimination studies in vivo were performed, and elimination parameters in perfused rat liver and kidney were determined. Biodistribution studies showed that (99m)Tc-Demogastrin 1 was rapidly cleared from the blood and most organs. A significant amount of radioactivity was detected in the CCK-2 receptor-rich organs, such as the stomach. Low radioactivity was found in the CCK-1 receptor-rich organs. Radioactivity in bowels and stomach declined relatively slowly. High and long-term retention of radioactivity in the kidneys was observed. Elimination of (99m)Tc-Demogastrin 1 via the bile was negligible. A high and rapid renal excretion was observed in elimination experiments in vivo. In the perfused kidney, glomerular filtration was found to be the main renal excretion mechanism of (99m)Tc-Demogastrin 1. Demogastrin 1 was distributed preferentially to the organs expressing CCK-2 receptors. The decisive elimination route of (99m)Tc-Demogastrin 1 in rats was urinary excretion. A high and prolonged renal retention may limit potential clinical use of the compound.
authors.affiliation: Faculty of Pharmacy, Charles University in Prague, Hradec Kralove, Czech Republic. trejtnarf@faf.cuni.cz
authors.forename: Frantisek
authors.initials: F
authors.lastname: Trejtnar
authors.forename: Alice
authors.initials: A
authors.lastname: Laznickova
authors.forename: Milan
authors.initials: M
authors.lastname: Laznicek
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Novy
authors.forename: Theodosia
authors.initials: T
authors.lastname: Maina
authors.forename: Berthold A
authors.initials: BA
authors.lastname: Nock
authors.forename: Martin
authors.initials: M
authors.lastname: Behe
mesh_terms: D000818:Animals; D005755:Gastrins / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B / Q000378:metabolism; D013667:Technetium / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D005755:Gastrins; D019275:Radiopharmaceuticals; D043887:Receptor, Cholecystokinin B; D013667:Technetium