In vivo characterizations of [11C]BMS193885 and [11C]Desmethyl-BMS193885 as a PET tracer for neuropeptide Y Y1 receptors

Background/Aims: Neuropeptide Y (NPY) has been implicated in a wide variety of physiological processes including feeding, learning and memory, emotion, cardiovascular homeostasis, hormone secretion, and circadian rhythms. NPY mediates these processes via interaction with a family of G-protein coupled receptors (NPY Y1, Y2, Y4 and Y5). NPY Yl receptor is the most widely studied among NPY receptors and is involved with many of these processes of NPY. BMS193885 was developed as a potent, selective NPY Y1 receptor antagonist (Ki = 3.3 nM [1]). To image the function of NPY Y1 receptor using PET, we developed 11C-labeled BMS193885 ([11C]BMS) and its O-desmethyl derivative ([11C]DMBMS) as a PET tracer. Methods: [11C]BMS was synthesized from [11C]methyl iodide using DMBMS. [11C]DMBMS was synthesized from [11C]phosgene using the aniline and amine derivatives. Biodistribution studies were conducted in mice. Animal studies were approved by the Animal Ethics Committee of the National Institutes for Quantum and Radiological Science and Technology. Results: In the radiosynthesis of [11C]BMS and [11C]DMBMS, the decay-corrected radiochemical yield from 11CO2 at the end of radionuclide production was 19-28% (n = 6) and 22-26% (n = 4), respectively. In the biodistribution at 60 min after the injection of [11C]BMS and [11C]DMBMS, radioactivity level was relatively high in the kidney, small intestine and liver, and was low in the brain. By pretreatment with BMS (10 mg/kg), the radioactivity levels of kidney, lung and spleen at 30 min after the injection of [11C]BMS were significantly reduced, and the radioactivity levels of these organs added heart at 30 min after the injection of [11C]DMBMS were significantly reduced. Conclusions: [11C]DMS and [11C]DMBMS were successfully synthesized as an injection. [11C]DMBMS showed the specific binding of NPY Y1 receptors rich organs (heart, kidney, lung and spleen) in mice.\nReferences: [1] Poindexter GS, et al. Bioorg Med Chem Lett. 2002;12:379-82. \n(Abstracts are to be no more than 300 words. References, Title and authors details are not included in the word count. Abstracts should not contain bullet points.)12th World Congress of the World Federation of Nuclear medicine and Biolog