Gao, MingzhangWang, MinGlick-Wilson, Barbara E.Meyer, Jill A.Peters, Jonathan S.Territo, Paul R.Green, Mark A.Hutchins, Gary D.Zarrinmayeh, HamidehZheng, Qi-Huang2018-12-192018-12-192019-02Gao, M., Wang, M., Glick-Wilson, B. E., Meyer, J. A., Peters, J. S., Territo, P. R., … Zheng, Q.-H. (2019). Synthesis and initial in vitro characterization of a new P2X7R radioligand [18F]IUR-1602. Applied Radiation and Isotopes, 144, 10–18. https://doi.org/10.1016/j.apradiso.2018.11.006https://hdl.handle.net/1805/18006The overexpression of P2X7R is associated with neuroinflammation and plays an important role in various neurodegenerative diseases. The [18F]fluoropropyl derivative of GSK1482160, [18F]IUR-1602, has been first prepared and examined as a new potential P2X7R radioligand. The reference standard IUR-1602 was synthesized from tert-butyl (S)-5-oxopyrrolidine-2-carboxylate, fluoropropylbromide, and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 13% in three steps. The target tracer [18F]IUR-1602 was synthesized from desmethyl-GSK1482160 with 3-[18F]fluoropropyl tosylate, prepared from propane-1,3-diyl bis(4-methylbenzenesulfonate) and K[18F]F/Kryptofix2.2.2, in two steps and isolated by HPLC combined with SPE in 2–7% decay corrected radiochemical yield. The radiochemical purity was >99%, and the molar activity at end of bombardment (EOB) was 74–370 GBq/μmol. The potency of IUR-1602 in comparison with GSK1482160 was determined by a radioligand competitive binding assay using [11C]GSK1482160, and the binding affinity Ki values for IUR-1602 and GSK1482160 are 23.6 and 3.07 nM, respectively. The initial in vitro evaluation results, 8-fold less potency of [18F]IUR-1602 compared to [11C]GSK1482160, prevent further in vivo evaluation of [18F]IUR-1602 in animals and human.enPublisher Policy[18F]IUR-1602 ((S)-N-(2-chloro-3-(trifluoromethyl)benzyl)-1-(2-[18F]fluoropropyl)-5-oxopyrrolidine-2-carboxamide)purinergic P2X7 receptor (P2X7R)radiosynthesisArticle