@article{oai:repo.qst.go.jp:00046205,
 author = {Kimura, Yasuyuki and et.al and 木村 泰之},
 issue = {10},
 journal = {Journal of Nuclear Medicine},
 month = {Oct},
 note = {Our laboratory developed 11C-NOP-1A, a new radioligand for the nociceptin/orphanin FQ peptide (NOP) receptor with high affinity (Ki = 0.15 nM) and appropriate lipophilicity (measured logD = 3.4) for PET brain imaging. Here, we assessed the utility of 11C-NOP-1A for quantifying NOP receptors in monkey brain and estimated the radiation safety profile of this radioligand based on its biodistribution in monkeys. Methods: Baseline and blocking PET scans were acquired from head to thigh on three rhesus monkeys for ~120 minutes after 11C-NOP-1A injection. These six PET scans were used to quantify NOP receptors in brain and to estimate radiation exposure to organs of the body. In the blocked scans, a selective nonradioactive NOP receptor antagonist (SB-612111; 1 mg/kg i.v.) was administered before 11C-NOP-1A. In all scans, arterial blood was sampled to measure the parent radioligand 11C-NOP-1A. Distribution volume (VT; a measure of receptor density) was calculated with a compartment model using brain and arterial plasma data. Radiation-absorbed doses were calculated using the Medical Internal Radiation Dose Committee scheme. Results: After 11C-NOP-1A injection, peak uptake of radioactivity in brain had a high concentration (~5 SUV), occurred early (~12 minutes), and thereafter washed out quickly. VT (mL · cm-3) was highest in neocortex (~20) and lowest in hypothalamus and cerebellum (~13). SB-612111 blocked ~50-70% of uptake and reduced VT in all brain regions to ~7 mL · cm-3. Distribution was well identified within 60 minutes of injection and stable for the remaining 60 minutes, consistent with only parent radioligand and not radiometabolites entering brain. Whole- body scans confirmed that the brain had specific (i.e., displaceable) binding but could not detect specific binding in peripheral organs. The effective dose for humans estimated from the baseline scans in monkeys was 5.0 microSv/MBq.
Conclusion: 11C-NOP-1A is a useful radioligand for quantifying NOP receptors in monkey brain, and its radiation dose is similar to that of other 11C-labeled ligands for neuroreceptors. 11C- NOP-1A appears to be a promising candidate for measuring NOP receptors in human brain.},
 pages = {1638--1645},
 title = {Brain and whole-body imaging in rhesus monkeys of 11C-NOP-1A, a promising PET radioligand for nociceptin/orphanin FQ peptide receptors},
 volume = {52},
 year = {2011}
}