Kinetic brain analysis and whole-body imaging in monkey of [11C]MNPA: a dopamine agonist radioligand.

With a view to future extension of the use of the agonist radioligand [(11)C]MNPA ([O-methyl-(11)C]2-methoxy-N-propylnorapomorphine) from animals to humans, we performed two positron emission tomography (PET) studies in monkeys. First, we assessed the ability to quantify the brain uptake of [(11)C]MNPA with compartmental modeling. Second, we estimated the radiation exposure of [(11)C]MNPA to human subjects based on whole-body imaging in monkeys. Brain PET scans were acquired for 90 min and included concurrent measurements of the plasma concentration of unchanged radioligand. Time-activity data from striatum and cerebellum were quantified with two methods, a reference tissue model and distribution volume. Whole-body PET scans were acquired for 120 min using four bed positions from head to mid thigh. Regions of interest were drawn on compressed planar whole-body images to identify organs with the highest radiation exposures. After injection of [(11)C]MNPA, the highest concentration of radioactivity in brain was in striatum, with lowest levels in cerebellum. Distribution volume was well identified with a two-tissue compartmental model and was quite stable from 60 to 90 min. Whole-body PET scans showed the organ with the highest radiation burden (muSv/MBq) was the urinary bladder wall (26.0), followed by lungs (22.5), gallbladder wall (21.9), and heart wall (16.1). With a 2.4-h voiding interval, the effective dose was 6.4 muSv/MBq (23.5 mrem/mCi). In conclusion, brain uptake of [(11)C]MNPA reflected the density of D(2/3) receptors, quantified relative to serial arterial measurements, and caused moderate to low radiation exposure.