@article {Kumar114P, author = {Anil Kumar and Hiroto Kuwabara and Andrew Horti and Mohab Alexander and Daniel Holt and Hayden Ravert and Yongjun Gao and Ayon Nandi and Arman Rahmim and Robert Dannals and Dean Wong}, title = {Comparison of new PET radiotracers for quantification of nicotinic acetylcholine receptors in the brain}, volume = {48}, number = {supplement 2}, pages = {114P--114P}, year = {2007}, publisher = {Society of Nuclear Medicine}, abstract = {387 Objectives: Relatively slow kinetics of available PET radioligands(e.g. 2FA) for α4β2 subtype cerebral nicotinic acetylcholine receptor(nAChRs),is a practical confounding factor (i.e. an infusion period of 6 hours with the bolus-plus-infusion scheme). We examined eight newly synthesized nAChR radioligands with improved brain kinetics on non-human primates. Methods: Eight radioligands which survived screening were studied on non-human primates (n=4) with a GE Advance{\textregistered} PET scanner (n=3) or High Resolution Research Tomograph{\textregistered} (n=5) under Saffan{\textregistered} anesthesia. Arterial blood samples were taken to generate time activity curves (TACs) in plasma with metabolite correction. A standard template of volumes of interest (VOIs, a total of 17 regions) including Thalamus (Th) and cerebellum (Cb), was spatially normalized to PET to obtain regional TACs. Regional Binding Potential (BP) were obtained by the multilinear reference tissue method with 2 parameters (MRTM2; Ichise et al., 2002) using Cb as the reference region. Results: Four radioligands (JHU85208, JHU85157, JHU15103, and JHU85270) reached a steady-state within one hour of a bolus injection (i.e., stable Th-Cb ratios over time), but showed relatively low BP values in Th (range: 0.66 {\textendash} 1.52). Two radioligands (JHU86328 and JHU86358) reached a near steady state around 90 min and showed relatively high BP values (Table). The remaining JHU86390 and (-)-[11C]methyl-IPHNMI-IPBB (Ding et al., 2006) showed slower kinetics. Active isomer of (-)-[11C]NMI-IPB methyl-IPHB was used in this study, while racemic mixture ({\textpm})-[11C]NMI-IPB was used in the original publication. (Ding et al., 2005) [table] Conclusions: Two radioligands (JHU86328 and JHU86358) showed relatively faster kinetics while maintaining reasonable BP values in cortical and subcortical regions. The findings warrant further investigations of the radioligands on the human brain to assess whether it is possible to resolve the above-mentioned practical confounding factor. Research Support (if any): Grant support: K24 DA00412 BP values in selected brain regions}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/48/supplement_2/114P.3}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }