Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
J Nucl Med. 2012 Sep;53(9):1471-80. doi: 10.2967/jnumed.112.103846. Epub 2012 Jul 31.
The PET radioligand 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ((18)F-nifene) is an α4β2* nicotinic acetylcholine receptor (nAChR) agonist developed to provide accelerated in vivo equilibrium compared with existing α4β2* radioligands. The goal of this work was to analyze the in vivo kinetic properties of (18)F-nifene with both kinetic modeling and graphical analysis techniques.
Dynamic PET experiments were performed on 4 rhesus monkeys (female; age range, 9-13 y) using a small-animal PET scanner. Studies began with a high-specific-activity (18)F-nifene injection, followed by a coinjection of (18)F-nifene and unlabeled nifene at 60 min. Sampling of arterial blood with metabolite analysis was performed throughout the experiment to provide a parent radioligand input function. In vivo kinetics were characterized with both a 1-tissue-compartment model (1TCM) and a 2-tissue-compartment model, Logan graphical methods (both with and without blood sampling), and the multilinear reference tissue model. Total distribution volumes and nondisplaceable binding potentials (BP(ND)) were used to compare regional binding of (18)F-nifene. Regions examined include the anteroventral thalamus, lateral geniculate body, frontal cortex, subiculum, and cerebellum.
The rapid uptake and binding of (18)F-nifene in nAChR-rich regions of the brain was appropriately modeled using the 1TCM. No evidence for specific binding of (18)F-nifene in the cerebellum was detected on the basis of the coinjection studies, suggesting the suitability of the cerebellum as a reference region. Total distribution volumes in the cerebellum were 6.91 ± 0.61 mL/cm(3). BP(ND) values calculated with the 1TCM were 1.60 ± 0.17, 1.35 ± 0.16, 0.26 ± 0.08, and 0.30 ± 0.07 in the anteroventral thalamus, lateral geniculate body, frontal cortex, and subiculum, respectively. For all brain regions, there was a less than 0.04 absolute difference in the average BP(ND) values calculated with each of the 1TCM, multilinear reference tissue model, and Logan methods.
The fast kinetic properties and specific regional binding of (18)F-nifene promote extension of the radioligand into preclinical animal models and human subjects.
使用动力学建模和图形分析技术分析（18）F-尼芬的体内动力学特性。
使用小动物 PET 扫描仪在 4 只恒河猴（♀；年龄范围，9-13 岁）上进行动态 PET 实验。研究开始时，进行高比活度（18）F-尼芬注射，60 分钟后进行（18）F-尼芬和未标记的尼芬的共注射。整个实验过程中通过代谢物分析对动脉血进行采样，以提供亲代放射性配体输入函数。使用 1 组织室模型（1TCM）和 2 组织室模型、Logan 图形方法（包括有和没有血液采样）以及多线性参考组织模型对体内动力学进行了特征描述。总分布容积和不可置换结合势（BP（ND））用于比较（18）F-尼芬在各个区域的结合情况。检查的区域包括前腹侧丘脑、外侧膝状体、额叶皮层、下托和小脑。
使用 1TCM 可以适当模拟（18）F-尼芬在富含烟碱型乙酰胆碱受体的脑区的快速摄取和结合。基于共注射研究，小脑未检测到（18）F-尼芬的特异性结合，这表明小脑适合作为参照区。小脑的总分布容积为 6.91±0.61mL/cm3。使用 1TCM 计算的 BP（ND）值分别为 1.60±0.17、1.35±0.16、0.26±0.08 和 0.30±0.07，在前腹侧丘脑、外侧膝状体、额叶皮层和下托。对于所有脑区，使用 1TCM、多线性参考组织模型和 Logan 方法计算的平均 BP（ND）值之间的差异小于 0.04。
（18）F-尼芬的快速动力学特性和特定的区域性结合促进了放射性配体在临床前动物模型和人体中的应用。
