[11C]Irinotecan was synthesized by two routes using [11C]phosgene and [11C]carbon dioxide fixation. Metabolites in the plasma of mice following injection of [11C] irinotecan were investigated using a combination of column-switching high-performance liquid chromatography (HPLC) and on-line solid-phase extraction (SPE). Whole-body PET studies were conducted in wild-type mice and P-glycoprotein and breast cancer resistance protein (Pgp/Bcrp) knockout mice.
[11C]Irinotecan was successfully synthesized by the two abovementioned routes. Decay-corrected radiochemical yields based on [11C]carbon dioxide using [11C]phosgene and [11C]carbon dioxide fixation were 8.8 ¡À 2.0 % (n = 8) and 16.9 ¡À 2.9 % (n = 5), respectively. Metabolite analysis of the plasma of mice following injection of [11C]irinotecan was successfully performed using the column-switching HPLC and on-line SPE combination resulting in greater than 87 % recovery of radioactivity from HPLC. In the PET study in mice, the radioactivity levels in the brain, liver, and small intestine were slightly increased by inhibition of the Pgp/Bcrp function for more than 30 min after [11C]irinotecan injection. This result demonstrated that in vivo behavior of [11C] irinotecan and radioactive metabolites are influenced by the Pgp/Bcrp function.
PET studies using [11C]irinotecan combined with metabolite analysis may be a useful tool for evaluating irinotecan pharmacokinetics and toxicity.