Synthesis and evaluation of a tridentate Tc-99m labeled long chain fatty acid analog for myocardial imaging

Long chain fatty acids serve as the main energy source for the myocardium. As an effort to develop Tc-99m labeled long chain fatty acid analogs due to ideal physical properties and ready availability of Tc-99m, we synthesized and evaluated a tridentate Tc-99m tricarbonyl-N2O-pentadecanoic acid ([Tc-99m]) as a novel radiotracer for myocardial imaging. The pyridinyl precursor of methyl pentadecanoate was prepared in high yield and reacted with [Tc-99m(CO)3(H2O)3]+ at 75 .deg. for 30 min, followed by hydrolysis in 0.4 N NaOH-MeOH. The resulting [Tc-99m] was purified by HPLC and redissolved in 5% ethanol-saline containing 5% bovine serum albumin. In vitro stability of [Tc-99m] was measured in human serum at 37 .deg. for 12 h using radio-TLC. Dynamic images were obtained in SD rats using a gamma camera. Re standard was synthesized as the synthesis of [Tc-99m] using [(NEt4)2[Re(CO)3CI3]. [Tc-99m] was synthesized in 70-78% radiochemical yield and with radiochemical purity higher than 98%. Re counterpart was used to identify the Tc-99m labeled fatty acid analog. [Tc-99m] was shown to be stable (>98%) over 12 h when incubated in human serum. Dynamic images showed rapid accumulation of the radioactivity in the liver, the heart. and the kidneys. ROIs were drawn in the liver and the heart, and their count/pixel ratios were obtained as 2.2:1, 7.5:1, and 16.5:1 at 1, 2 and 5 min postinjection, respectively. There was no significant uptake in the thyroid or salivary gland, indicating that Tc-99m pertechnetate was not regenerated during the time of the study. The results demonstrated that [Tc-99m] may be useful for myocardial imaging. Further studies are warranted to perform tissue distribution of [Tc-99m] in mice