Cerebral uptake of 11C—Ro 15—1788 and its acid metabolite 11C—Ro 15—3890; PET study in healthy volunteers

The benzodiazepine antagonist Ro 15–1788 and its acid metabolic product Ro 15–3890 were labelled with ¹¹C and used in a PET study to examine their ability to penetrate the blood-brain barrier in man. After intravenous administration to healthy volunteers, ¹¹C-Ro 15–1788 immediately accumulated to a large extent in the brain, where about 5 per cent of the dose injected was still present after 20 min. ¹¹C-Ro 15–3890, on the other hand, did not accumulate significantly in the central nervous system. At 20 min after the injection less than 0·1 per cent of the radioactivity injected was present in the brain. The results allow the conclusion that the acid metabolite of Ro 15–1788 formed by peripheral metabolism does not significantly contribute to brain radioactivity levels after intravenous injection of ¹¹C-Ro 15–1788 to man. The results also demonstrate the potential of the PET technique to analyse pharmacokinetic aspects of drug transport into the central nervous system in man.