TY - JOUR T1 - <sup>18</sup>F-Nifrolene-microPET studies of nicotinic α4β2 receptors JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 219 LP - 219 VL - 51 IS - supplement 2 AU - Kenney Vu AU - Evgueni Sevrioukov AU - Cristian Constantinescu AU - Min-Liang Pan AU - Rama Pichika AU - Jogesh Mukherjee Y1 - 2010/05/01 UR - http://jnm.snmjournals.org/content/51/supplement_2/219.abstract N2 - 219 Objectives Imaging thalamic and extrathalamic nicotinic α4β2 receptors is important to study tobacco dependence, cognitive deficits in Alzheimer’s disease and other brain functions. We have previously reported MicroPET studies using 18F-Nifene, a high affinity agonist PET tracer (Ki = 0.50 nM for α4β2) with fast kinetics of binding. We now report MicroPET rodent studies using a high affinity antagonist, 18F-Nifrolene (Ki = 0.36 nM for α4β2). Methods 18F-Nifrolene and 18F-Nifene were synthesized as previously reported. Male Sprague Dawley rats (~400-600 g) anesthetized with isoflurane were used. Test-retest studies were carried out after iv 18F-Nifrolene and 18F-Nifene (0.3 to 0.9 mCi) in order to evaluate reproducibility. Rats were imaged for up to 120 mins and binding potential (BPND) was measured. Post-18F-Nifrolene or 18F-Nifene nicotine challenge was used to measure reversibility. Data was analyzed using ASIPRO and PMOD programs. In vitro, brain sections (10 μm) were treated with 18F-Nifrolene with concentrations ~2-3μCi/cc, incubated for 60 min at 37°C, washed (2x2 min cold buffer, water rinse), air dried and exposed to phosphor screens. Results 18F-Nifrolene binding to thalamic and extrathalamic brain regions was consistent with the α4β2 nicotinic receptors distribution in rat brain measured in vitro studies and was similar to that of 18F-Nifene. Kinetics of binding of 18F-Nifrolene were slower, reaching pseudoequilibrium ~90 mins compared to 18F-Nifene which is ~50-60 mins. Using reference cerebellum, thalamus to cerebellum ratios for 18F-Nifrolene were ~3 which is similar to that for 18F-Nifene. Ratios of thalamus to cerebellum in vitro was ~12. Postinjection of nicotine (0.3 mg/kg, +30 min) rapidly displaced specifically bound radiotracer. Conclusions 18F-Nifrolene appears suitable for MicroPET studies of nicotinic α4β2 in the rodent brain. Research Support NIH R01 AG02947 ER -