[(18)F]Fluoroacetate is not a functional analogue of [(11)C]acetate in normal physiology.

PURPOSE: [(11)C]Acetate (C-AC) is a general PET tracer of cellular carbon flux and useful for clinical imaging in heart disease as well as prostate cancer and other tumours. C-AC has a high (70%) whole-body extraction fraction, proportional to blood flow in many organs. Trapping is related to organ-specific enzymatic activation and formation of [(11)C]-acetyl-CoA, the fate of which has been well characterized. Due to the logistic challenges with C-AC, 2-[(18)F]fluoroacetate (F-AC) has been proposed as a marker for prostate cancer imaging. METHOD: We evaluated the potential of F-AC as a tracer for imaging blood flow and early enzymatic steps in the intermediary metabolism. C-AC and F-AC were injected serially in three cynomolgus monkeys and one domestic pig and scanned using PET/CT. A dynamic scan covering heart and liver was followed by repeated whole-body imaging. Kinetic patterns were compared for the myocardium, liver, blood and other organs. RESULTS: C-AC kinetics and organ distribution in both species were similar to those previously established in man. In contrast, F-AC showed prolonged blood retention, no detectable trapping in myocardium or salivary glands, rapid clearance from liver and extensive excretion to bile and urine. Massive defluorination was seen in the pig, resulting in intense skeletal activity. CONCLUSION: 2-[(18)F]Fluoroacetate cannot be regarded as a functional analogue of 1-[(11)C]acetate in normal physiology and appears to be of little use for studies of organ blood flow, intermediary metabolism or lipid synthesis.