Distribution, Elimination, and Renal Handling of (99m)Technetium-Demogastrin 1

作者：Trejtnar Frantisek^*; Laznickova Alice; Laznicek Milan; Novy Zbynek; Maina Theodosia; Nock Berthold A; Behe Martin

来源：Cancer Biotherapy and Radiopharmaceuticals, 2012, 27(2): 169-174.

DOI：10.1089/cbr.2011.1008

• receptor-specific peptides
• CCK/gastrin receptors
• pharmacokinetics
• renal excretion
• liver excretion

Radiolabeled cholecystokinin/gastrin (CCK) receptor-targeting peptides are promising compounds for radio-diagnosis and radiotherapy of certain malignancies. This study evaluated the pharmacokinetic profile of a CCK-2 receptor-specific peptide, Demogastrin 1, labeled with technetium-99m (Tc-99m-Demogastrin 1), in rats. To investigate the fate of Tc-99m-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 Tc-99m-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 Tc-99m-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 Tc-99m-Demogastrin 1. Demogastrin 1 was distributed preferentially to the organs expressing CCK-2 receptors. The decisive elimination route of Tc-99m-Demogastrin 1 in rats was urinary excretion. A high and prolonged renal retention may limit potential clinical use of the compound.

• 出版日期2012-3