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.

• MeSH
• gastriny farmakokinetika   MeSH
• izotopové značení metody   MeSH
• játra metabolismus   MeSH
• krysa rodu rattus MeSH
• ledviny metabolismus   MeSH
• potkani Wistar MeSH
• radiofarmaka farmakokinetika   MeSH
• receptor cholecystokininu B metabolismus   MeSH
• technecium farmakokinetika   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Due to their high CCK-2/gastrin receptor selectivity, high affinity, and rapid background clearance, radiolabeled minigastrins (MG) are emerging as promising new tools in the diagnosis and therapy of CCK-2/gastrin receptor-positive tumors. In this study, the pharmacokinetic profile, particularly the excretion mode, of two 111In-labeled minigastrins was compared in rats. The first tracer, 111In-MG-0 is based on (D)Glu1-MG, while the second, 111In-MG-11, is its des-(Glu)5-derivative, expected to be less retained in renal tissue. MATERIALS AND METHODS: The fate of 111In-MG-0 and 111In-MG-11 in the body of rats was investigated during biodistribution and bioelimination experiments, while the respective elimination parameters were determined in perfused rat liver and kidney models. RESULTS: During biodistribution both compounds were rapidly cleared from the blood and most non-target organs whereas activity levels in the bowel and stomach declined slowly. The overall contribution of hepatobiliary excretion of 111In-MG-0 and 111In-MG-11 was relatively small. In the perfused rat liver their elimination into the bile was negligible. In contrast, renal excretion was the major excretion pathway for both analogs, mainly via glomerular filtration. However, kidney levels were substantially higher and retention was more prolonged in the case of 111In-MG-0 as compared to 111In-MG-11. CONCLUSION: The presence of the (Glu)5-chain in 111Ln-MG-0 appears to be implicated in the prolonged radioactivity retention in the kidney of rats.

• MeSH
• cholecystokinin metabolismus   MeSH
• financování organizované MeSH
• gastriny farmakokinetika   MeSH
• izotopové značení MeSH
• játra metabolismus   MeSH
• krysa rodu rattus MeSH
• ledviny metabolismus   MeSH
• oligopeptidy farmakokinetika   MeSH
• peptidové fragmenty metabolismus   MeSH
• perfuze MeSH
• potkani Wistar MeSH
• radiofarmaka farmakokinetika   MeSH
• radioizotopy india diagnostické užití   MeSH
• receptor cholecystokininu B metabolismus   MeSH
• substrátová specifita MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH