Initial human PET imaging studies with the dopamine transporter ligand 18F-FECNT.
Initial human PET imaging studies with the dopamine transporter ligand 18F-FECNT.
复制标题
DOI：
--
复制
发表时间：
2003-06
期刊：
影响因子：
--
通讯作者：
M. Davis;J. Votaw;J. Bremner;M. Byas-Smith;T. Faber;R. Voll;J. Hoffman;Scott T. Grafton;C. Kilts;M. Goodman
中科院分区：
文献类型：
--
作者：
M. Davis;J. Votaw;J. Bremner;M. Byas-Smith;T. Faber;R. Voll;J. Hoffman;Scott T. Grafton;C. Kilts;M. Goodman
本研究的目的是初步评估2- β -碳甲氧基-3 - β -（4-氯苯基）-8-（2-(18)f -氟乙基）nortropane ((18)F-FECNT) PET扫描在确定健康人和帕金森病（PD）患者体内脑多巴胺转运体（DAT）密度方面的有用性。方法选取神经系统健康者6例和PD患者5例，其中单侧轻度病变2例，双侧轻中度病变1例，双侧中重度病变2例。健康受试者进行3小时PET扫描（26帧），PD受试者进行2小时PET扫描（23帧），同时在扫描的前5分钟注射F-FECNT。在整个扫描过程中采集动脉血液样本进行well-counter和代谢物分析，以确定可能存在的活性代谢物。重建扫描；然后我们在每个受试者的尾状核、壳核、丘脑、脑干、小脑和枕叶皮层放置感兴趣的球体区域。每个区域的放射性水平是根据受试者PET扫描的每一帧来计算的。然后我们计算每个时间段的目标组织与小脑的比率。结果动脉血样品分析显示示踪剂代谢迅速。动脉输入的醚萃取成分为>98%纯（18）F-FECNT。尾状核和壳核对放射性配体的吸收和保留时间最长。他们都在大约90分钟时达到最大摄取，健康受试者的尾状核和壳核与小脑的平均比值（+/- sd）当时分别为9.0 +/- 1.2和7.8 +/- 0.7。健康受试者尾状核与小脑的最大比值为7.6 ~ 10.5，壳核与小脑的最大比值为7.1 ~ 9.3。2例早期单侧PD患者在90 min时，右侧尾状核与小脑的平均比值为5.3 +/- 1.1，左侧比值为5.9 +/- 0.7，右侧壳核与小脑的平均比值为2.8 +/- 0.1，左侧比值为3.0 +/- 0.6。晚期PD患者在90 min时，右侧尾状核与小脑的平均比值为3.7 +/- 0.4，左侧比值为3.9 +/- 0；右侧壳核与小脑的平均比值为1.8 +/- 0.1，左侧比值为1.8 +/- 0。结论（18）F-FECNT是一种用于人体DAT系统体内成像的极好的候选放射配体。与5 -羟色胺转运体相比，它对DAT具有更高的亲和力，并产生最高的纹状体与小脑比率，并且具有（18）f放射性标记DAT配体中最有利的动力学。在我们的早期（单侧）PD患者中发现了身体未受影响一侧对面半球的症状前变化，似乎与其他DAT放射配位体一样，它可能能够识别症状前PD。
UNLABELLED The aim of this study was to do an initial assessment of the usefulness of 2beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(2-(18)F-fluoroethyl)nortropane ((18)F-FECNT) PET scanning in determining in vivo brain dopamine transporter (DAT) density in healthy humans and subjects with Parkinson's disease (PD). METHODS We investigated 6 neurologically healthy subjects and 5 PD patients: 2 with mild unilateral disease, 1 with mild-to-moderate bilateral disease, and 2 with moderately severe bilateral disease. The healthy subjects underwent a 3-h PET scan (26 frames) and the PD subjects underwent a 2-h PET scan (23 frames) while (18)F-FECNT was being injected over the first 5 min of the scan. Arterial blood samples were taken throughout scanning for well-counter and metabolite analysis to determine the presence of possible active metabolites. The scans were reconstructed; then we placed spheric regions of interest in the caudate nuclei, putamena, thalami, brain stem, cerebellum, and occipital cortex of each subject. The radioactivity level in each region was calculated for each frame of a subject's PET scan. Then we calculated target tissue-to-cerebellum ratios for each time frame. RESULTS The analysis of arterial blood samples revealed that metabolism of the tracer was rapid. The ether-extractable component of the arterial input was >98% pure (18)F-FECNT. The caudate nucleus and putamen exhibited the highest uptake and prolonged retention of the radioligand. They both attained maximum uptake at approximately 90 min, with the healthy subjects' average caudate- and putamen-to-cerebellum ratios (+/-SD) at that time being 9.0 +/- 1.2 and 7.8 +/- 0.7, respectively. The maximal caudate-to-cerebellum ratios for the healthy subjects ranged from 7.6 to 10.5 and their maximal putamen-to-cerebellum ratios ranged from 7.1 to 9.3. The 2 early-stage, unilateral PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 5.3 +/- 1.1 and a left ratio of 5.9 +/- 0.7 and an average right putamen-to cerebellum ratio of 2.8 +/- 0.1 and a left ratio of 3.0 +/- 0.6. The late-stage PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 3.7 +/- 0.4 and a left ratio of 3.9 +/- 0 and an average right putamen-to cerebellum ratio of 1.8 +/- 0.1 and a left ratio of 1.8 +/- 0. CONCLUSION These results indicate that (18)F-FECNT is an excellent candidate radioligand for in vivo imaging of the DAT system in humans. It has a much higher affinity for DAT than for the serotonin transporter and yields the highest peak striatum-to-cerebellum ratios and has among the most favorable kinetics of (18)F-radiolabeled DAT ligands. Having picked up presymptomatic changes in the hemisphere opposite the unaffected side of the body in our early-stage (unilateral) PD patients, it appears that, like other DAT radioligands, it may be able to identify presymptomatic PD.