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Preliminary Evaluation of 15-[¹⁸F]Fluoro-3-oxa-pentadecanoate as a PET Tracer of Hepatic Fatty Acid Oxidation

Departments of Radiology and Medicine, Duke University Medical Center, Durham, North Carolina

View larger version (15K): [in this window] [in a new window]   FIGURE 1. Chemical structures of 18F-labeled fatty acids.

View larger version (10K): [in this window] [in a new window]   FIGURE 2. Two-compartment model for fitting FOP kinetics in isolated rat liver. Cp is radioactivity concentration in input perfusate; C1 and C2 represent first and second tissue compartments, respectively; and k1–k4 are rate constants.

View larger version (15K): [in this window] [in a new window]   FIGURE 3. Tissue-to-blood 18F radioactivity concentration ratios for FOP in healthy living rats. Each data point represents mean and SD for group of 3–4 rats killed at given time.

View larger version (20K): [in this window] [in a new window]   FIGURE 4. Reverse-phase HPLC analysis of FOP standard (A) and 18F radioactivity in representative samples of serum taken from control or etomoxir-treated rats 15 min after injection of FOP (B and C). Small levels of unidentified polar metabolites of FOP were observed in serum samples. Intact FOP composed 85.4% ± 1.4% and 96.7% ± 0.8% (P < 0.0001) of total radioactivity in serum 15 min after injection for control and etomoxir-treated rats, respectively.

View larger version (14K): [in this window] [in a new window]   FIGURE 5. Characteristic time–activity curves for FOP in isolated rat livers. Livers were perfused in normoxic (95% O2) or hypoxic (15% O2) conditions. Livers were pulse perfused with radiotracer in perfusate at constant concentration over the interval 0–20 min, followed by 20-min washout.

View larger version (17K): [in this window] [in a new window]   FIGURE 6. Two-compartment model fit to 18F radioactivity kinetics in normoxic isolated rat liver administered FOP as 20-min pulse followed by 20-min washout. Measured kinetics were successfully fit by model, showing no significant discrepancies between data and model curves besides statistical counting noise. k1–k4 are rate constants.

View larger version (17K): [in this window] [in a new window]   FIGURE 7. Relationship of estimates of DVs of FOP to FPOR in isolated rat liver. Each experiment is represented by single data point on each graph. Both normoxic (95% O2) data (•) and hypoxic (15% O2) data () are shown.