This article is a US government work and, as such, is in the public domain in the United States of America.
Kinetic brain analysis and whole-body imaging in monkey of [11C]MNPA: A dopamine agonist radioligand†
Article first published online: 19 JUN 2008
Published © 2008 Wiley-Liss, Inc.
Volume 62, Issue 9, pages 700–709, September 2008
How to Cite
Seneca, N., Skinbjerg, M., Zoghbi, S. S., Liow, J.-S., Gladding, R. L., Hong, J., Kannan, P., Tuan, E., Sibley, D. R., Halldin, C., Pike, V. W. and Innis, R. B. (2008), Kinetic brain analysis and whole-body imaging in monkey of [11C]MNPA: A dopamine agonist radioligand. Synapse, 62: 700–709. doi: 10.1002/syn.20544
- Issue published online: 24 JUN 2008
- Article first published online: 19 JUN 2008
- Manuscript Accepted: 14 MAR 2008
- Manuscript Received: 9 JAN 2008
- Intramural Program (National Institute of Mental Health). Grant Number: Z01-MH-002795-06
- DA D2/3 receptor agonist radioligand;
- whole-body biodistribution;
- kinetic analysis
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.