Whole-body distribution and metabolism of [N-methyl-11C](R)-1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinolinecarboxamide in humans; an imaging agent for in vivo assessment of peripheral benzodiazepine receptor activity with positron emission tomography

Purpose   ¹¹C-PK11195 is a radiopharmaceutical for in vivo assessment of peripheral benzodiazepine receptor (PBR) activity using PET. We sought to clarify the metabolic fate of ¹¹C-PK11195 in a test–retest setting using radio-HPLC in comparison with radio-TLC, and the whole-body distribution in humans. Materials and methods  In order to evaluate the reproducibility of radio-HPLC metabolite analyses, ten patients with Alzheimer’s disease (AD) underwent two successive ¹¹C-PK11195 examinations on separate days. For comparison of different analytical methods, plasma samples from seven patients were also analysed by radio-TLC. In addition, we evaluated the whole-body distribution of ¹¹C-PK11195 and its uptake in the brain. Results  The level of unmetabolized ¹¹C-PK11195 decreased slowly from 96.3 ± 1.6% (mean±SD) at 5 min to 62.7 ± 8.3% at 40 min after injection. Large individual variation was observed in the amount of plasma ¹¹C-PK11195 radiometabolites. The whole-body distribution of ¹¹C-PK11195 showed the highest radioactivity levels in urinary bladder, adrenal gland, liver, salivary glands, heart, kidneys, and vertebral column. In addition, the hip bone and breast bone were clearly visualized by PET. In patients with AD, ¹¹C-PK11195 uptake in the brain was the highest in the basal ganglia and thalamus, followed by the cortical grey matter regions and the cerebellum. Low ¹¹C-PK11195 uptake was observed in the white matter. Conclusion  Our results indicate that ¹¹C-PK11195 is eliminated both through the renal and hepatobiliary systems. Careful analysis of plasma metabolites is required to determine the accurate arterial input function for quantitative PET measurement.