Effect of monounsaturation of a branched fatty acid on organ selectivity.
1-[11C]-3-R,S-methylheptadecanoic acid (BMHA) is a branched chain fatty acid analog that is transported into the myocardium. Due to incomplete metabolism, however, radiolabeled products are trapped within myocytes. Recently, we demonstrated that this compound is an excellent tracer to monitor fatty acid metabolism.


METHODS
To evaluate the effect of mono-unsaturation on myocardial substrate utilization, we prepared 1-[11C]-3-R,S-methyl-trans--heptadec-7-enoic acid (t-7-BMHA) and measured its biodistribution in rats. In addition, preliminary PET studies were performed on dogs.


RESULTS
Biodistribution studies demonstrated that 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 ratios were 4.43 compared to 1.09. The heart-to-blood ratio of t-7-BMHA was greater than 11:1. PET imaging with 1-[11C]-t-7-BMHA demonstrated high myocardial extraction, prolonged retention of radioactivity and excellent image quality. Accumulation of radioactivity in the myocardium reached a plateau within 10 min postinjection, with heart-to-blood ratios exceeding 20:1 and heart-to-lung ratios exceeding 10:1. Blood clearance of radioactivity was biphasic with half-times of 1.46 and 14.7 min, respectively.


CONCLUSIONS
These data suggest that introduction of a trans-double bond in BMHA improves myocardial selectivity and results in a potentially superior imaging agent.
D000818:Animals; D002250:Carbon Radioisotopes; D004285:Dogs; D005227:Fatty Acids / Q000737:chemistry / Q000493:pharmacokinetics; D005229:Fatty Acids, Monounsaturated / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D006321:Heart / Q000000981:diagnostic imaging*; D008099:Liver / Q000000981:diagnostic imaging; D008168:Lung / Q000000981:diagnostic imaging; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
C096532:3-methylheptadec-7-enoic acid; D002250:Carbon Radioisotopes; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; C033637:3-methylheptadecanoic acid