Synthesis and evaluation of a new fluorine-18 labeled rotenoid as a potential pet probe of mitochondrial complex I activity.

Fluorine-18 labeled (6aS, 12aS, 5'R)-12-deoxo-6',7'-dihydro-7'-fluororote ( F-DDRT), a new potential PET probe of mitochondrial complex I activity, was synthesized. [F-18]-DDRT was prepared with good specific activity by nucle ophilic displacement with an overall radiochemical yield of 25% (EOB). The uptake of [F-18]-DDRT in rat brain and heart was compared with the uptake o f another fluorine-18 labeled rotenoid: [F-18]-DHRT. In comparison to [F-18 ]-DHRT, the brain and heart retention of [F-18]-DDRT were both lower at any point of the study (respectively 0.49 and 2.82% dose/g vs 0.34 and 1.24% d ose/g at 60 min post injection).