Abstract
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.