Brain and Whole-Body Imaging in Rhesus Monkeys of 11C-NOP-1A a Promising PET Radioligand for Nociceptin/Orphanin FQ Peptide Receptors

摘要

Our laboratory developed (S)-3-(2′-fluoro-6′,7′-dihydrospiro [piperidine-4,4′-thieno[3,2-c]pyran]-1-yl)-2-(2-fluorobenzyl)-N-methylpropanamide (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 the monkey brain and estimated the radiation safety profile of this radioligand based on its biodistribution in monkeys.MethodsBaseline and blocking PET scans were acquired from head to thigh for 3 rhesus monkeys for approximately 120 min after ¹¹C-NOP-1A injection. These 6 PET scans were used to quantify NOP receptors in the 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 intravenously) 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 MIRD Committee scheme.