学术探索
学术期刊
新闻热点
数据分析
智能评审

6-[18F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors

被引：41
作者：
Horti, AG
Chefer, SI
Mukhin, AG
Koren, AO
Gündisch, D
Links, JM
Kurian, V
Dannals, RF
London, ED
机构：
[1] NIDA, Brain Imaging Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA
[2] Johns Hopkins Med Inst, Div Nucl Med, Baltimore, MD 21205 USA
[3] Johns Hopkins Med Inst, Div Radiat Hlth Sci, Baltimore, MD 21205 USA
来源：
LIFE SCIENCES | 2000年 / 67卷 / 04期
基金：
美国国家卫生研究院;
关键词：
nicotinic acetylcholine receptor; positron emission tomography (nAChRs); 6-[F-18]fluoro-3-(2(S)-azetidinyl-methoxy)pyridine; (6-[F-18]fluoro-A-85380; 6-[F-18]FA);
D O I：
10.1016/S0024-3205(00)00635-4
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
A novel positron emission tomography (PET) radiotracer, 6-[F-18]fluoro-3-(2(S)-azetidinyl-methoxy)pyridine (6-[F-18]fluoro-A-85380, 6-[F-18]FA) was synthesized by a no-carrier-added fluorination, In 6-[F-18]FA bound to nicotinic acetylcholine receptors (nAChRs), with very high affinity (K-d 28 PM). In PET studies, 6-[F-18]FA specifically labeled central nAChRs in the brain of the Rhesus monkey and demonstrated highest levels of accumulation of radioactivity in brain regions enriched with the a,Pz subtype of nAChR, 6-[F-18]FA exhibited a target-to-non-target ratio (estimated as radioactivity in the thalamus to that in the cerebellum) of binding in primate brain similar to that previously determined for a labeled analog of epibatidine, [F-18]FPH. In contrast to [F-18]FPH, the novel tracer is expected to exhibit substantially less toxicity. Thus, the novel radioligand, 6-[18F]FA, appears to be a suitable candidate for imaging nAChRs in human brain. Published by Elsevier Science Inc.
引用
收藏
页码：PL463 / PL469
页数：7
相关论文
共 26 条
[1]   Novel 3-pyridyl ethers with subnanomolar affinity for central neuronal nicotinic acetylcholine receptors [J].
Abreo, MA ;
Lin, NH ;
Garvey, DS ;
Gunn, DE ;
Hettinger, AM ;
Wasicak, JT ;
Pavlik, PA ;
Martin, YC ;
DonnellyRoberts, DL ;
Anderson, DJ ;
Sullivan, JP ;
Williams, M ;
Americ, SP ;
Holladay, MW .
JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (04) :817-825
[2]   Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors [J].
Bannon, AW ;
Decker, MW ;
Holladay, MW ;
Curzon, P ;
Donnelly-Roberts, D ;
Puttfarcken, PS ;
Bitner, RS ;
Diaz, A ;
Dickenson, AH ;
Porsolt, RD ;
Williams, M ;
Arneric, SP .
SCIENCE, 1998, 279 (5347) :77-81
[3]   2-[18F]F-A-85380:: a PET radioligand for α4β2 nicotinic acetylcholine receptors [J].
Chefer, SI ;
Horti, AG ;
Koren, AO ;
Gündisch, D ;
Links, JM ;
Kurian, V ;
Dannals, RF ;
Mukhin, AG ;
London, ED .
NEUROREPORT, 1999, 10 (13) :2715-2721
[4]   In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85380 using single photon emission computed tomography [J].
Chefer, SI ;
Horti, AG ;
Lee, KS ;
Koren, AO ;
Jones, DW ;
Gorey, JG ;
Links, JM ;
Mukhin, AG ;
Weinberger, DR ;
London, ED .
LIFE SCIENCES, 1998, 63 (25) :PL355-PL360
[5]  
Ding YS, 1996, SYNAPSE, V24, P403
[6]   EVIDENCE IN POSTMORTEM BRAIN-TISSUE FOR DECREASED NUMBERS OF HIPPOCAMPAL NICOTINIC RECEPTORS IN SCHIZOPHRENIA [J].
FREEDMAN, R ;
HALL, M ;
ADLER, LE ;
LEONARD, S .
BIOLOGICAL PSYCHIATRY, 1995, 38 (01) :22-33
[7]   Neuronal nicotinic acetylcholine receptors as targets for drug discovery [J].
Holladay, MW ;
Dart, MJ ;
Lynch, JK .
JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (26) :4169-4194
[8]  
Horti A, 1996, J LABELLED COMPD RAD, V38, P355, DOI 10.1002/(SICI)1099-1344(199604)38:4<355::AID-JLCR842>3.0.CO
[9]  
2-3
[10]  
Horti AG, 1998, J LABELLED COMPD RAD, V41, P309, DOI 10.1002/(SICI)1099-1344(199804)41:4<309::AID-JLCR78>3.0.CO
123