Technetium-99m-Labeled Medium-Chain Fatty Acid Analogues Metabolized by β-Oxidation: Radiopharmaceutical for Assessing Liver Function

External imaging of energy production activity of living cells with 99mTc-labeled compounds is a challenging task requiring good design of 99mTc-radiopharmaceuticals. On the basis of our recent findings that 11C- and 123I-labeled medium-chain fatty acids are useful for measuring β-oxidation activity...

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Bibliographic Details
Published in:Bioconjugate chemistry 1999-05, Vol.10 (3), p.489-495
Main Authors: Yamamura, Norio, Magata, Yasuhiro, Arano, Yasushi, Kawaguchi, Takayoshi, Ogawa, Kazuma, Konishi, Junji, Saji, Hideo
Format: Article
Language:English
Subjects:
Animals
Cysteine - chemistry
Fatty Acids - chemistry
Fatty Acids - metabolism
Liver - drug effects
Liver - metabolism
Liver Function Tests
Male
Oxidation-Reduction
Radiopharmaceuticals - chemistry
Radiopharmaceuticals - metabolism
Rats
Rats, Wistar
Technetium - chemistry
Technetium - metabolism
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Summary:External imaging of energy production activity of living cells with 99mTc-labeled compounds is a challenging task requiring good design of 99mTc-radiopharmaceuticals. On the basis of our recent findings that 11C- and 123I-labeled medium-chain fatty acids are useful for measuring β-oxidation activity of hepatocytes, we focused on development of 99mTc-labeled medium-chain fatty acid analogues that reflect β-oxidation activity of the liver. In the present study, monoamine−monoamide dithiol (MAMA) ligand and triamido thiol (MAG) ligand were chosen as chelating groups because of the stability and size of their complexes with 99mTc and their ease of synthesis. Each ligand was attached to the ω-position of hexanoic acid (MAMA-HA and MAG-HA, respectively). In biodistribution studies, [99mTc]MAMA-HA showed high initial accumulation in the liver followed by clearance of the radioactivity in the urine. Analysis of the urine revealed [99mTc]MAMA-BA as the sole radiometabolite. Furthermore, when [99mTc]MAMA-HA was incubated with living liver slices, generation of [99mTc]MAMA-BA was observed. However, [99mTc]MAMA-HA remained intact when the compound was incubated with liver slices in the presence of 2-bromooctanoate, an inhibitor of β-oxidation. The findings in this study indicated that [99mTc]MAMA-HA was metabolized by β-oxidation after incorporation into the liver. On the other hand, poor hepatic accumulation was observed after administration of [99mTc]MAG-HA.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc9801528