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

• Published in: Synapse (New York, N.Y.) Vol. 62; no. 9; pp. 700 - 709
• Main Authors: Seneca, Nicholas, Skinbjerg, Mette, Zoghbi, Sami S., Liow, Jeih-San, Gladding, Robert L., Hong, Jinsoo, Kannan, Pavitra, Tuan, Edward, Sibley, David R., Halldin, Christer, Pike, Victor W., Innis, Robert B.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2008
• Subjects: [11C]MNPA; Animals; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes - blood; Carbon Radioisotopes - pharmacokinetics; DA D2/3 receptor agonist radioligand; dosimetry; kinetic analysis; Macaca mulatta; Magnetic Resonance Imaging; Male; Naproxen - blood; Naproxen - pharmacokinetics; PET; Positron-Emission Tomography - methods; Radiometry; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D3 - metabolism; Tissue Distribution; Whole Body Imaging; whole-body biodistribution
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.20544

With a view to future extension of the use of the agonist radioligand [11C]MNPA ([O‐methyl‐11C]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 [11C]MNPA with compartmental modeling. Second, we estimated the radiation exposure of [11C]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 [11C]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 (μSv/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 μSv/MBq (23.5 mrem/mCi). In conclusion, brain uptake of [11C]MNPA reflected the density of D2/3 receptors, quantified relative to serial arterial measurements, and caused moderate to low radiation exposure. Synapse 62:700–708, 2008. Published 2008 Wiley‐Liss, Inc.