CardioPET, a potential PET tracer for coronary artery disease, exhibits higher heart-to-liver ratios in fed mice and rats

Objectives CardioPET (trans-9-[¹⁸F]fluoro-3,4-methyleneheptadecanoic acid), a modified fatty acid closely resembling naturally-occurring free fatty acids, undergoes metabolic trapping in heart tissue. As with other tracers of mitochondrial fatty acid oxidation in the heart, competing liver uptake is a problem. In this study, the pharmacokinetic behavior of CardioPET was evaluated in fed and fasted mice and rats.

Methods Biodistribution of CardioPET was determined in fed and fasted male ( CD-1, 25-28 grams ) mice and ( CD, 175-200 grams) rats at 60min (n = 6). One set of animals were fed Prolab 5P76 Isopro RMS 3000 lab chow ad libtum until injection of CardioPET. Another set of animals were fasted 24 h prior to injection of the tracer. The animals were euthanized by C02 overdose and subjected to complete necroscopy. Tissues were weighed and counted using a Wizard gamma-counter and results were expressed as %dose/gram tissue mean +/- SEM.

Results Fed mice: at 60 min, tracer accumulation (%DPG) was 14.4% heart and 4.4% liver and 1.2% blood. In fasted mice tracer uptake was 4.5% heart, 15.8% liver and 1.7% blood. Fed rats: accumulation was 2.2% heart and 3.3% liver and 0.3% blood. In fasted rats tracer uptake was 0.8% heart, 5.5% liver and 0.4% blood.

Conclusions Heart/liver ratios of CardioPET in fed mice and rats are dramatically improved compared to that of the fasted animals. This reversal in ratios indicates hepatic fatty acid oxidation and trapping of CardioPET can be suppressed under fed conditions which would improve heart imaging.