Choi Jae Yong, Lyoo Chul Hyoung, Kim Jin Su, Kim Kyeong Min, Kang Jee Hae, Choi Soo-Hee, Kim Jae-Jin, Ryu Young Hoon
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
PLoS One. 2015 Apr 1;10(4):e0121342. doi: 10.1371/journal.pone.0121342. eCollection 2015.
The purpose of this research is to evaluate the prospects for the use of 4-(trans-18F-fluoranylmethyl)-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide (18F-Mefway) in comparison to 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (18F-FCWAY) for the quantification of 5-HT1A receptors in human subjects.
Five healthy male controls were included for two positron emission tomography (PET) studies: 18F-FCWAY PET after the pretreatment with 500 mg of disulfiram and two months later, 18F-Mefway PET without disulfiram. Regional time-activity curves (TACs) were extracted from nine cortical and subcortical regions in dynamic PET images. Using cerebellar cortex without vermis as reference tissue, in vivo kinetics for both radioligands were compared based on the distribution volume ratio (DVR) calculated by non-invasive Logan graphical analysis and area under the curve ratio of the TACs (AUC ratio).
Although the pattern of regional uptakes in the 18F-Mefway PET was similar to that of the 18F-FCWAY PET (highest in the hippocampus and lowest in the cerebellar cortex), the amount of regional uptake in 18F-Mefway PET was almost half of that in 18F-FCWAY PET. The skull uptake in 18F-Mefway PET was only 25% of that in 18F-FCWAY PET with disulfiram pretreatment. The regional DVR values and AUC ratio values for 18F-Mefway were 17-40% lower than those of 18F-FCWAY. In contrast to a small overestimation of DVR values by AUC ratio values (< 10%) in 18F-FCWAY PET, the overestimation bias of AUC ratio values was much higher (up to 21%) in 18F-Mefway PET.
As 18F-Mefway showed lower DVR values and greater overestimation bias of AUC ratio values, 18F-Mefway may appear less favorable than 18F-FCWAY. However, in contrast to 18F-FCWAY, the resistance to in vivo defluorination of 18F-Mefway obviates the need for the use of a defluorination inhibitor. Thus, 18F-Mefway may be a good candidate PET radioligand for 5-HT1A receptor imaging in human.
本研究的目的是评估4-(反式-18F-氟甲基)-N-[2-[4-(2-甲氧基苯基)哌嗪-1-基]乙基]-N-吡啶-2-基环己烷-1-甲酰胺（18F-Mefway）与18F-反式-4-氟-N-2-[4-(2-甲氧基苯基)哌嗪-1-基]乙基]-N-(2-吡啶基)环己烷甲酰胺（18F-FCWAY）相比，在人体定量5-HT1A受体方面的应用前景。
纳入5名健康男性对照进行两项正电子发射断层扫描（PET）研究：在500mg双硫仑预处理后进行18F-FCWAY PET，两个月后进行无双硫仑的18F-Mefway PET。从动态PET图像中的9个皮质和皮质下区域提取区域时间-活性曲线（TAC）。以无蚓部的小脑皮质作为参考组织，基于通过非侵入性洛根图形分析计算的分布体积比（DVR）和TAC的曲线下面积比（AUC比），比较两种放射性配体的体内动力学。
尽管18F-Mefway PET的区域摄取模式与18F-FCWAY PET相似（海马摄取最高，小脑皮质摄取最低），但18F-Mefway PET的区域摄取量几乎是18F-FCWAY PET的一半。18F-Mefway PET中的颅骨摄取仅为经双硫仑预处理的18F-FCWAY PET的25%。18F-Mefway的区域DVR值和AUC比值比18F-FCWAY低17 - 40%。与18F-FCWAY PET中AUC比值对DVR值的轻微高估（<10%）相反，18F-Mefway PET中AUC比值的高估偏差要高得多（高达21%）。
由于18F-Mefway显示出较低的DVR值和较高的AUC比值高估偏差，18F-Mefway可能不如18F-FCWAY有利。然而，与18F-FCWAY不同，18F-Mefway对体内脱氟的抗性消除了使用脱氟抑制剂的必要性。因此，18F-Mefway可能是人体5-HT1A受体成像的良好候选PET放射性配体。
