title: 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.
authors.affiliation: Turku PET Centre, Turku University Central Hospital, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Roivainen
authors.forename: S
authors.initials: S
authors.lastname: Forsback
authors.forename: T
authors.initials: T
authors.lastname: Grönroos
authors.forename: P
authors.initials: P
authors.lastname: Lehikoinen
authors.forename: M
authors.initials: M
authors.lastname: Kähkönen
authors.forename: E
authors.initials: E
authors.lastname: Sutinen
authors.forename: H
authors.initials: H
authors.lastname: Minn
mesh_terms: D000818:Animals; D001622:Betaine / Q000097:blood; D002250:Carbon Radioisotopes; D002794:Choline / Q000031:analogs & derivatives* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006801:Humans; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; C017506:methylcholine; D001622:Betaine; D002794:Choline