16-Cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid:: Synthesis and evaluation of fatty acid metabolism in mouse myocardium

We synthesized 16-cyclopentadienyl tricarbonyl (99m)Tc 16-oxo-hexadecanoic acid ((99m)Tc-CpTT-16-oxo-HDA, 1) and investigated its potential as a radiotracer for evaluating fatty acid metabolism in myocardium. Radiotracer 1 was synthesized in 22.6 +/- 6.3% decay-corrected yield by a double ligand transfer reaction between the ferrocene adduct of methyl hexadecanoate (2) and Na(99m)TcO(4) in the presence of Cr(CO)(6) and CrCl(3), followed by hydrolysis of the methyl ester group. Radiotracer 1 was found to be chemically stable (99% at 6 h) when incubated in human serum. A tissue distribution study in mice showed that high radioactivity accumulated in heart (9.03%ID/g at 1 min and 5.41% ID/g at 5 min postinjection) with rapid clearance and that heart to blood uptake ratios increased with time (2.13 at 5 min and 3.76 at 30 min postinjection). Metabolite analysis of the heart tissues using a simple extraction method showed that (99m)Tc-CpTT-4-oxo-butyric acid was detected as the major radioactive metabolite by HPLC, suggesting that 1 is metabolized to (99m)Tc-CpTT-4-oxo-butyric acid via beta-oxidation in myocardium.