用于NK1受体定量的强效、选择性、放射性标记的P物质拮抗剂（[18F]SPA-RQ）的合成与表征
Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK1 receptor quantitation: ([18F]SPA-RQ).
作者信息
Solin Olof, Eskola Olli, Hamill Terence G, Bergman Jörgen, Lehikoinen Pertti, Grönroos Tove, Forsback Sarita, Haaparanta Merja, Viljanen Tapio, Ryan Christine, Gibson Raymond, Kieczykowski Gerard, Hietala Jarmo, Hargreaves Richard, Burns H Donald
机构信息
Turku PET Centre, Turku, Finland.
出版信息
Mol Imaging Biol. 2004 Nov-Dec;6(6):373-84. doi: 10.1016/j.mibio.2004.08.001.
PURPOSE
To develop and characterize a radiolabelled Substance-P antagonist useful for quantitation of neurokinin-1 receptors in the brain via PET imaging.
PROCEDURE
[18F]SPA-RQ (Substance-P antagonist - receptor quantifier) was synthesized in good yield and high specific activity by alkylation of a BOC protected phenolate anion using [18F]bromofluoromethane. Removal of the BOC protecting group with trifluoroacetic acid gave [18F]SPA-RQ.
RESULTS
SPA-RQ has high affinity for human, rhesus monkey and guinea pig NK1 receptors (h-IC50=67 pM) and has a log P value of 1.8. Biodistribution studies in guinea pig showed that this tracer penetrates the blood-brain barrier and selectively labels NK1 receptors in the striatum and cortex.
CONCLUSION
[18F]SPA-RQ is a potent, high affinity Substance-P antagonist that can be conveniently labeled with high specific activity using [18F]fluoromethylbromide. This tracer is a useful tool for noninvasive imaging of central NK1 receptors.
目的
开发并表征一种放射性标记的P物质拮抗剂，用于通过正电子发射断层扫描（PET）成像定量脑内神经激肽-1（NK1）受体。
程序
通过使用[18F]溴氟甲烷对BOC保护的酚盐阴离子进行烷基化反应，以良好的产率和高比活度合成了[18F]SPA-RQ（P物质拮抗剂-受体定量剂）。用三氟乙酸除去BOC保护基团得到[18F]SPA-RQ。
结果
SPA-RQ对人、恒河猴和豚鼠的NK1受体具有高亲和力（h-IC50 = 67 pM），log P值为1.8。豚鼠体内的生物分布研究表明，该示踪剂可穿透血脑屏障，并选择性地标记纹状体和皮质中的NK1受体。
结论
[18F]SPA-RQ是一种强效、高亲和力的P物质拮抗剂，可使用[18F]氟甲基溴方便地进行高比活度标记。该示踪剂是用于中枢NK1受体无创成像的有用工具。
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