Technetium-99m-Labeled Medium-Chain Fatty Acid Analogues Metabolized by -Oxidation: Radiopharmaceutical for Assessing
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- 作者：Norio Yamamura ; Yasuhiro Magata ; Yasushi Arano ; Takayoshi Kawaguchi ; Kazuma Ogawa ; Junji Konishi ; and Hideo Saji
- 刊名：Bioconjugate Chemistry
- 出版年：1999
- 出版时间：May 1999
- 年：1999
- 卷：10
- 期：3
- 页码：489 - 495
- 全文大小：122K
- 年卷期：v.10,no.3(May 1999)
- ISSN：1520-4812
文摘
External imaging of energy production activity of living cells with 99mTc-labeled compounds is achallenging task requiring good design of 99mTc-radiopharmaceuticals. On the basis of our recentfindings that 11C- and 123I-labeled medium-chain fatty acids are useful for measuring 
-oxidationactivity of hepatocytes, we focused on development of 99mTc-labeled medium-chain fatty acid analoguesthat reflect -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 thestability and size of their complexes with 99mTc and their ease of synthesis. Each ligand was attachedto the 
-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 theradioactivity 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 wasincubated with liver slices in the presence of 2-bromooctanoate, an inhibitor of -oxidation. The findingsin this study indicated that [99mTc]MAMA-HA was metabolized by -oxidation after incorporation intothe liver. On the other hand, poor hepatic accumulation was observed after administration of [99mTc]MAG-HA.
-oxidationactivity of hepatocytes, we focused on development of 99mTc-labeled medium-chain fatty acid analoguesthat reflect -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 thestability and size of their complexes with 99mTc and their ease of synthesis. Each ligand was attachedto the -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 theradioactivity 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 wasincubated with liver slices in the presence of 2-bromooctanoate, an inhibitor of -oxidation. The findingsin this study indicated that [99mTc]MAMA-HA was metabolized by -oxidation after incorporation intothe liver. On the other hand, poor hepatic accumulation was observed after administration of [99mTc]MAG-HA.