Blood metabolism of [methyl-C-11]choline; implications for in vivo imagingwith positron emission tomography

[methyl-C-11] Choline (C-11-choline) is a radioligand potentially useful fo r oncological positron emission tomography (PET). As a first step towards t he development of a kinetic model for quantification of C-11-choline uptake , blood metabolism of C-11-choline during PET imaging was studied in humans . High-performance liquid chromatography (HPLC) and thin-layer chromatograp hy (TLC) were used for the analysis of C-11-choline and its radioactive met abolites. Prior to human PET imaging we studied ex vivo the biodistribution and metabolism of intravenously administered C-11-choline in rats. Our res ults revealed that the radioactivity accumulated particularly in kidney. lu ng, adrenal gland and liver. Chromatographic analysis showed that the level of unmetabolized C-11-choline in rat plasma decreased from 42%+/-20% (mean +/-SD) at 5 min to 21%+/-10% at 15 min after injection. In accordance with these findings, in humans the unmetabolized C-11-choline represents 62%+/-1 9% of the total radioactivity in arterial plasma at 5 min after injection a nd 27%+/-12% at 15 min. In human venous plasma the corresponding values wer e 85%+/-12% and 48%+/-12% at 5 and 10 min, respectively. The major metaboli te observed in both human and rat plasma was identified as C-11-betaine, In human arterial plasma this maximally represented 82%+/-9% of the total rad ioactivity at 25 min after radiotracer injection. By 20 min after injection , the C-11-choline and C-11-betaine in human arterial plasma reached a plat eau, and their fractional activities remained nearly constant thereafter. A lthough most of the circulating C-11-choline in blood is transported to tis sues, it does not disappear totally from blood within the first 40 min afte r tracer injection.