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.
Seneca
Nicholas
N
Molecular Imaging Branch, National Institute of Mental Health, Building 31, Bethesda, MD 20892, USA. nicholasseneca@mail.nih.gov
Skinbjerg
Mette
M
Zoghbi
Sami S
SS
Liow
Jeih-San
JS
Gladding
Robert L
RL
Hong
Jinsoo
J
Kannan
Pavitra
P
Tuan
Edward
E
Sibley
David R
DR
Halldin
Christer
C
Pike
Victor W
VW
Innis
Robert B
RB
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D009288:Naproxen / Q000097:blood / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011874:Radiometry; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D014018:Tissue Distribution; D051598:Whole Body Imaging
D002250:Carbon Radioisotopes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D009288:Naproxen