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

Abstract.

[methyl-¹¹C]Choline (¹¹C-choline) is a radioligand potentially useful for oncological positron emission tomography (PET). As a first step towards the development of a kinetic model for quantification of ¹¹C-choline uptake, blood metabolism of ¹¹C-choline during PET imaging was studied in humans. High-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) were used for the analysis of ¹¹C-choline and its radioactive metabolites. Prior to human PET imaging we studied ex vivo the biodistribution and metabolism of intravenously administered ¹¹C-choline in rats. Our results revealed that the radioactivity accumulated particularly in kidney, lung, adrenal gland and liver. Chromatographic analysis showed that the level of unmetabolized ¹¹C-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 ¹¹C-choline represents 62%±19% of the total radioactivity in arterial plasma at 5 min after injection and 27%±12% at 15 min. In human venous plasma the corresponding values were 85%±12% and 48%±12% at 5 and 10 min, respectively. The major metabolite observed in both human and rat plasma was identified as ¹¹C-betaine. In human arterial plasma this maximally represented 82%±9% of the total radioactivity at 25 min after radiotracer injection. By 20 min after injection, the ¹¹C-choline and ¹¹C-betaine in human arterial plasma reached a plateau, and their fractional activities remained nearly constant thereafter. Although most of the circulating ¹¹C-choline in blood is transported to tissues, it does not disappear totally from blood within the first 40 min after tracer injection.