Evaluation of F-nifene binding to α4β2 nicotinic receptors in the rat brain using microPET imaging.
Evaluation of F-nifene binding to α4β2 nicotinic receptors in the rat brain using microPET imaging.
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DOI：
10.1186/2191-219x-1-6
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发表时间：
2011-06-01
期刊：
影响因子：
3.2
通讯作者：
Mukherjee J
中科院分区：
文献类型：
--
作者：
Kant R;Constantinescu CC;Parekh P;Pandey SK;Pan ML;Easwaramoorthy B;Mukherjee J
用18F-nifene（一种新的正电子发射断层扫描（PET）放射性示踪剂）对大鼠烟碱乙酰胆碱能受体（nAChR）α4β2受体进行了MicroPET成像研究。在静脉内注射18F-尼芬（0.8至1 mCi）后对大鼠成像90分钟，并测量结合电位（BPND）。18F-Nifene与丘脑和丘脑外脑区的结合与大鼠脑中α4β2 nAChR的分布一致。使用小脑作为参考，丘脑的值变化小于5%（BPND = 1.30，n = 3），证实了18F-尼芬结合的再现性。还使用18F-Nifene microPET成像来评估尼古丁在异氟烷麻醉下的一组Sprague-Dawley大鼠中的作用。尼古丁的挑战后，管理的18 F-尼芬证明可逆的18 F-尼芬结合在体内。对于α4β2 nAChR受体占有率（nAChROCC），在18 F-尼芬给药前15分钟给予不同剂量的尼古丁（0、0.02、0.1、0.25和0.50 mg/kg尼古丁游离碱）。低剂量尼古丁（0.02 mg）达到> 80% nAChROCC，而在较高剂量（0.25 mg）下测量到> 90% nAChROCC。参考小脑的少量18F-尼芬结合影响nAChROCC的准确评价。目前正在努力确定啮齿动物18F-nifene microPET研究的替代参考区域。
MicroPET imaging studies using 18F-nifene, a new positron emission tomography (PET) radiotracer for nicotinic acetylcholinergic receptors (nAChR) α4β2 receptors in rats, have been carried out. Rats were imaged for 90 min after intravenous injection of 18F-nifene (0.8 to 1 mCi), and binding potential (BPND) was measured. 18F-Nifene binding to thalamic and extrathalamic brain regions was consistent with the α4β2 nAChR distribution in the rat brain. Using the cerebellum as a reference, the values for the thalamus varied less than 5% (BPND = 1.30, n = 3), confirming reproducibility of 18F-nifene binding. 18F-Nifene microPET imaging was also used to evaluate effects of nicotine in a group of Sprague-Dawley rats under isoflurane anesthesia. Nicotine challenge postadministration of 18F-nifene demonstrated reversibility of 18F-nifene binding in vivo. For α4β2 nAChR receptor occupancy (nAChROCC), various doses of nicotine (0, 0.02, 0.1, 0.25, and 0.50 mg/kg nicotine free base) 15 min prior to 18F-nifene were administered. Low-dose nicotine (0.02 mg) reached > 80% nAChROCC while at higher doses (0.25 mg) > 90% nAChROCC was measured. The small amount of 18F-nifene binding with reference to the cerebellum affects an accurate evaluation of nAChROCC. Efforts are underway to identify alternate reference regions for 18F-nifene microPET studies in rodents.