title: A Tc-99m-labeled long chain fatty acid derivative for myocardial imaging.
abstract: C-11- and I-123-labeled long chain fatty acid derivatives have been reported as useful radiopharmaceuticals for the estimation of myocardial fatty acid metabolism. We have reported that Tc-99m-labeled N-[[[(2-mercaptoethyl)amino]carbonyl]methyl]-N-(2-mercaptoethyl)-6-aminohexanoic acid ([(99m)Tc]MAMA-HA), a medium chain fatty acid derivative, is metabolized by beta-oxidation in the liver and that the MAMA ligand is useful for attaching to the omega-position of fatty acid derivatives as a chelating group for Tc-99m. On the basis of these findings, we focused on developing a Tc-99m-labeled long chain fatty acid derivative that reflected fatty acid metabolism in the myocardium. In this study, we synthesized a dodecanoic acid derivative, MAMA-DA, and a hexadecanoic acid derivative, MAMA-HDA, and performed radiolabeling and biodistribution studies. [(99m)Tc]MAMA-DA and [(99m)Tc]MAMA-HDA were prepared using a ligand-exchange reaction. Biodistribution studies were carried out in normal mice and rats. Then, a high initial uptake of Tc-99m was observed, followed by a rapid clearance from the heart. The maximum heart/blood ratio was 3.6 at 2 min postinjection of [(99m)Tc]MAMA-HDA. These kinetics were similar to those with postinjection of p-[(125)I]iodophenylpentadecanoic acid. Metabolite analysis showed [(99m)Tc]MAMA-HDA was metabolized by beta-oxidation in the body. In conclusion, [(99m)Tc]MAMA-HDA is a promising compound as a long chain fatty acid analogue for estimating beta-oxidation of fatty acid in the heart.
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. magata@hama-med.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Magata
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Misa
authors.initials: M
authors.lastname: Ukon
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamura
authors.forename: Tomoya
authors.initials: T
authors.lastname: Uehara
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ogawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Arano
authors.forename: Takashi
authors.initials: T
authors.lastname: Temma
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
authors.forename: Eiji
authors.initials: E
authors.lastname: Tadamura
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D005227:Fatty Acids / Q000652:urine; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D051379:Mice; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium / Q000652:urine; D014018:Tissue Distribution
chemical_list: D005227:Fatty Acids; D013667:Technetium