EFFECT OF MONOUNSATURATION OF A BRANCHED FATTY-ACID ON ORGAN SELECTIVITY

1-[C-11]-3-R,S-methylheptadecanoic acid (BMHA) is a branched chain fat ty acid analog that is transported into the myocardium. Due to incompl ete metabolism, however, radiolabeled products are trapped within myoc ytes. Recently, we demonstrated that this compound is an excellent tra cer to monitor fatty acid metabolism. Method: To evaluate the effect o f mono-unsaturation on myocardial substrate utilization, we prepared 1 -[C-11]-3-R,S-methyl-trans-heptadec-7-enoic acid (t-7-BMHA) and measur ed its biodistribution in rats. In addition, preliminary PET studies w ere performed on dogs. Results: Biodistribution studies demonstrated t hat myocardial-to-lung and myocardial-to-blood ratios for t-7-BMHA are higher than those for BMHA. Fifteen minutes after injection, heart-to -lung ratios were 5.23 compared to 2.92 and heart-to-liver ratios were 3.07 compared to 1.41 for t-7-BMHA and BMHA. By 30 min postinjection heart-to-lung ratios were 7.03 compared to 5.88 and heart-to-liver rat ios were 4.43 compared to 1.09. The heart-to-blood ratio of t-7-BMHA w as greater than 11:1. PET imaging with 1-[C-11]-t-7-BMHA demonstrated high myocardial extraction, prolonged retention of radioactivity and e xcellent image quality. Accumulation of radioactivity in the myocardiu m reached a plateau within 10 min postinjection, with heart-to-blood r atios exceeding 20:1 and heart-to-lung ratios exceeding 10:1. Blood cl earance of radioactivity was biphasic with half-times of 1.46 and 14.7 min, respectively. Conclusion: These data suggest that introduction o f a trans-double bond in BMHA improves myocardial selectivity and resu lts in a potentially superior imaging agent.