Kepe Vladimir, Barrio Jorge R, Huang Sung-Cheng, Ercoli Linda, Siddarth Prabha, Shoghi-Jadid Kooresh, Cole Gregory M, Satyamurthy Nagichettiar, Cummings Jeffrey L, Small Gary W, Phelps Michael E
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):702-7. doi: 10.1073/pnas.0510237103. Epub 2006 Jan 9.
4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide, a selective serotonin 1A (5-HT(1A)) molecular imaging probe, was used in conjunction with positron emission tomography (PET) for quantification of 5-HT(1A) receptor densities in the living brains of Alzheimer's disease patients (ADs) (n = 8), subjects with mild cognitive impairment (n = 6), and controls (n = 5). ADs had receptor densities significantly decreased in both hippocampi (binding potential: controls 1.62 +/- 0.07; ADs 1.18 +/- 0.26) and also in raphe nuclei (controls 0.63 +/- 0.09; ADs 0.37 +/- 0.20). When volume losses are included, 5-HT(1A) losses are even more severe (i.e., average mean decreases of 24% in mild cognitive impairment patients and 49% in ADs). A strong correlation of 5-HT(1A) receptor decreases in hippocampus with worsening of clinical symptoms (Mini Mental State Exam scores) was also found. Moreover, these decreases in 5-HT(1A) receptor measures correlate with decreased glucose utilization as measured with 2-deoxy-2-[F-18]fluoro-d-glucose PET in the brains of ADs (standardized uptake values; globally: controls 0.89 +/- 0.04, ADs 0.72 +/- 0.04; posterior cingulate gyrus: controls 1.05 +/- 0.09, ADs 0.79 +/- 0.11). They also inversely correlate with increased neuropathological loads measured with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile PET in several neocortical regions in the same subjects. The in vivo observations were confirmed independently by in vitro digital autoradiography with 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide and 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene)malononitrile on brain tissue specimens from two ADs and three nondemented subjects.
4-[F-18]氟-N-{2-[4-(2-甲氧基苯基)-1-哌嗪基]乙基}-N-(2-吡啶基)苯甲酰胺，一种选择性5-羟色胺1A（5-HT(1A)）分子成像探针，与正电子发射断层扫描（PET）联合使用，用于定量阿尔茨海默病患者（AD，n = 8）、轻度认知障碍受试者（n = 6）和对照组（n = 5）活体大脑中的5-HT(1A)受体密度。AD患者双侧海马体的受体密度显著降低（结合潜能：对照组1.62±0.07；AD患者1.18±0.26），中缝核也降低（对照组0.63±0.09；AD患者0.37±0.20）。若将体积损失考虑在内，5-HT(1A)的损失更为严重（即轻度认知障碍患者平均降低24%，AD患者平均降低49%）。还发现海马体中5-HT(1A)受体减少与临床症状恶化（简易精神状态检查评分）密切相关。此外，AD患者大脑中5-HT(1A)受体测量值的这些降低与用2-脱氧-2-[F-18]氟-D-葡萄糖PET测量的葡萄糖利用率降低相关（标准化摄取值；整体：对照组0.89±0.04，AD患者0.72±0.04；后扣带回：对照组1.05±0.09，AD患者0.79±0.11）。它们还与同一受试者几个新皮质区域用2-(1-{6-[(2-[F-18]氟乙基)(甲基)氨基]-2-萘基}亚乙基)丙二腈PET测量的神经病理学负荷增加呈负相关。体内观察结果通过对两名AD患者和三名非痴呆受试者的脑组织标本进行4-[F-18]氟-N-{2-[4-(2-甲氧基苯基)-1-哌嗪基]乙基}-N-(2-吡啶基)苯甲酰胺和2-(1-{6-[(2-[F-18]氟乙基)(甲基)氨基]-2-萘基}亚乙基)丙二腈的体外数字放射自显影得到独立证实。
