Muzic R F, Berridge M S, Friedland R P, Zhu N, Nelson A D
Department of Radiology, Case Western Reserve University, Cleveland, Ohio, USA.
J Nucl Med. 1998 Dec;39(12):2048-54.
Previous work on the PET measured uptake of (S)-[11C]nicotine presents conflicting findings as to whether it reflects specific binding.
We studied the uptake of (R)-[11C]nicotine and (S)-[11C]nicotine in normal volunteers at baseline conditions and after a challenge with unlabeled (S)-nicotine to decrease the concentration of free binding sites or with CO2 to increase perfusion. We analyzed the data using two- and three-compartment models.
We found tissue pharmacokinetics of (R)- and (S)-[11C]nicotine are adequately described by the two-compartment model. (S)-nicotine challenge induced small but statistically significant reductions in distribution volume (DV) of both (R)- and (S)-[11C]nicotine. The changes in DV could not be attributed to perfusion changes because DV was not affected by CO2 challenge. Although the reduction in DV indicates sensitivity of [11C]nicotine to status of nicotinic binding sites, the small magnitude of the reduction suggests that most nicotine uptake is nonspecific.
Although differences in DV attributable to specific binding were detected, (R)- and (S)-[11C]nicotine are relatively poor tracers for studying nicotinic binding sites using PET.
先前关于正电子发射断层扫描（PET）测量的（S）-[11C]尼古丁摄取的研究，对于它是否反映特异性结合存在相互矛盾的结果。
我们研究了正常志愿者在基线条件下以及在用未标记的（S）-尼古丁激发以降低游离结合位点浓度或用二氧化碳激发以增加灌注后，（R）-[11C]尼古丁和（S）-[11C]尼古丁的摄取情况。我们使用二室和三室模型分析数据。
我们发现二室模型能充分描述（R）-和（S）-[11C]尼古丁的组织药代动力学。（S）-尼古丁激发导致（R）-和（S）-[11C]尼古丁的分布容积（DV）均出现微小但具有统计学意义的降低。DV的变化不能归因于灌注变化，因为DV不受二氧化碳激发的影响。尽管DV的降低表明[11C]尼古丁对烟碱结合位点状态敏感，但降低幅度较小表明大多数尼古丁摄取是非特异性的。
尽管检测到了归因于特异性结合的DV差异，但（R）-和（S）-[11C]尼古丁在使用PET研究烟碱结合位点方面是相对较差的示踪剂。
