Labeled plasma metabolites of L-methyl-hydrogen-3-methionine and L-methyl-carbon-14-methionine in the dog

The validity of the mathematical models that attempt to describe positron emission tomography (PET) images produced with [¹¹CH₃] methionine in terms of rates of local cerebral protein synthesis has yet to be established. A major objection to current models is that the use of methionine labeled at the methyl position results in the dispersal of the label among various methyl-accepting compounds that appear in the plasma and may then enter the brain. One approach to overcoming this problem has been the use of 'standard' corrections for the activity contributed to plasma by labeled plasma protein and labeled serine. In order to determine the validity of this approach, the metabolic fate of labeled methionine was studied in six dogs. After injection with either [C³H₃]methionine or [¹⁴CH₃]methionine arterial blood was sampled. Plasma fractions containing protein were separated by fast gel filtration, counted with standard scintillation techniques, and their radioactivity was compared with total plasma radioactivity. Plasma was also separated by high-pressure liquid chromatography into methionine, serine, and nonmethionine or serine-containing fractions. These fractions were counted, and their radioactivity was compared with total plasma radioactivity. Labeled protein appeared in plasma about 20 minutes postinjection and then increased steadily. Labeled serine also appeared and reached a peak value of 9.4 ± 2.1% of plasma activity at 40 minutes. Of greatest interest was the appearance in later plasma samples of increasing amounts of activity contained in nonserine low molecular weight metabolites of methionine. At 40 minutes, those metabolites made up 27 ± 6.9% of total plasma activity. The data thus clearly indicate that a correction for serine alone does not adequately account for the activity contributed to plasma by low molecular weight metabolites of methionine. We suggest that tracer kinetic models should take the contribution of the nonserine metabolites into account.