Comparison of uptake of CardioPET, a potential PET tracer for myocardial fatty acid utilization and BFPET, a possible PET blood flow marker in fed vs fasted mice

Objectives CardioPET (trans-9-[^18F]fluoro-3,4-methyleneheptadecanoic acid), a modified fatty acid closely resembling naturally-occurring free fatty acids, undergoes metabolic trapping at the first step of beta-oxidation in heart tissue. Previously we observed that fasting decreased cardiac uptake of CardioPET in mice. In the present study we compared cardiac uptake of CardioPET and BFPET (4-[¹⁸F]fluorophenyltriphenylphosphonium, a PET blood flow marker, in fed and fasted mice.

Methods All studies were performed with male CD-1 mice weighing 25-30 grams (Charles River, Boston MA). Groups of eight animals were studied in the fed and fasted state. The fed mice were maintained on Prolab 5P76 Isopro RMS 3000 lab chow ad libitum until tracer injection. The fasted animals had no access to food for 24 hr prior to tracer injection. Each animal was injected with ~ 50 μCi of CardioPET or BFPET. The animals treated with CardioPET were sacrificed at 60 min. after tracer administration whereas the BFPET animals were sacrificed at 90 min. Radioactivity in myocardial tissue was measured with a well-type gamma counter and results were expressed as percent injected dose per gram (%ID/g, mean ± sem.

Results In fed mice, CardioPET accumulation (%ID/g) was 14.4±1.23% in the myocardium whereas in fasted mice CardioPET uptake in the heart was markedly reduced to 4.5±0.37% (p<0.0001). However, in both fed and fasted mice, cardiac uptake of BFPET was not significantly different (10.48 ± 0.61 vs 11.10 ± 0.86 mean ± SEM.

Conclusions The reduction in cardiac uptake of CardioPET produced by fasting in mice is not related to reduced myocardial uptake of BFPET, but is probably related to increased hepatic uptake in the fasting condition.

Research Support Shriners Hospitals For Childre