TY - JOUR T1 - In vivo study of a PET radiotracer for imaging P2X7 receptors for neuroinflammation in animal model JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 164 LP - 164 VL - 57 IS - supplement 2 AU - Junbin Han AU - Hongjun Jin AU - Hui Liu AU - Chunling Liu AU - Xuyi Yue AU - Zhude Tu Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/164.abstract N2 - 164Objectives The purinergic receptor P2X ligand-gated ion channel type 7 (P2X7-receptor) is expressed in glial cells and modulates neurophysiology via release of the proinflammatory cytokine interleukin (IL)-1β, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7Rs provides an inflammatory stimulus, and P2X7 receptor-deficient mice display a marked attenuation of inflammatory responses, including models of neuropathic and chronic inflammatory pain. Recently, [11C]GSK1482160 was reported as a promising PET tracer (IC50 = 3 nm) for imaging P2X7, but lack of detail in vivo characterization in animal models of neuroinflamation.1,2 To explore the possibility of imaging P2X7 receptor for neuroinflammation, [11C]GSK1482160 was radiosynthesized and performed initial in vivo evaluation in a neuroinflammation mice model and microPET studies were performed in in non-human primates (NHP).Methods [11C]GSK1482160 was synthesized by N-methylation of the corresponding amide with [11C]CH3OTf produced by in house built system. C57BL/6 mice were pre-injected using a single intraperitoneal injection of lipopolysaccharide (LPS) at dose of dose of 20 mg/kg body weight. Biodistribution study was performed for the LPS pretreated C57BL/6 (n=4) and sham control C57BL/6 mice n=4). MicroPET studies were performed in male cynomolgus monkeys (4-6 Kg) using a microPET Focus 220 scanner (Concorde/CTI/Siemens Microsystems).Results [11C]GSK1482160 was synthesized with high chemical (>95%) and radiochemical (>99%) purities, and good specific activity (about 1 Ci/mol, EOS) with a yield of 30-45%. Biodistribution studies revealed that [11C]GSK1482160 can penetrate the rodent brain. Compared with sham mice, tracer uptake in the brain of LPS pretreated mice have 2-fold higher than the sham control mice. MicroPET studies in nonhuman primates revealed that this tracer is able to cross blood brain barrier and have good accumulation in the brain with homogeneous distribution.Conclusions [11C]GSK1482160 has high potential to be radiotracer for investigating the expression of P2X7 receptors response to neuorinflammation. Further investigation of this tracer’s in vivo specificity and suitability in different neuroimflamation animal models is undergoing currently. Research support: DOE/NINDS/NIMH: DESC0012737&R01NS075527&MH092797 ER -