Preclinical evaluation of [¹¹C]NE40, a type 2 cannabinoid receptor PET tracer

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• 作者：Nele Evens^a ; ¹ ; Caroline Vandeputte^b ; ^c ; ¹ ; Charlotte Coolen^a ; Peter Janssen^d ; Raf Sciot^e ; Veerle Baekelandt^f ; Alfons M. Verbruggen^a ; Zeger Debyser^c ; ^f ; Koen Van Laere^b ; ^c ; Guy M. Bormans^a ; ^c ; ^{guy.bormans@pharm.kuleuven.be}
• 关键词：[11C]NE40 ; Type 2 cannabinoid receptor ; PET ; Neuroinflammation
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 期刊代码：43_09698051
• 类别：ph
• 出版时间：April, 2012
• 卷：39
• 期：3
• 页码：389-399
• 文件大小：977 K

摘要

Introduction

Up-regulation of the type 2 cannabinoid receptor (CB₂R) has been reported in (neuro)inflammatory diseases. In this study, we report the preclinical evaluation of [¹¹C]NE40 as positron emission tomography (PET) radioligand for visualization of the CB₂R.

Methods

The selectivity of NE40 for CB₂R and its toxicity and mutagenicity were determined. [¹¹C]NE40 was evaluated by biodistribution and autoradiography studies in normal rats and a microPET study in normal mice, rats and a rhesus monkey. Specific in vivo binding of [¹¹C]NE40 to human CB₂R (hCB₂R) was studied in a rat model with hCB₂R overexpression.

Results

[¹¹C]NE40 shows specific CB₂R binding in the spleen and blood of normal rats and high brain uptake in rhesus monkey. [¹¹C]NE40 showed specific and reversible binding to hCB₂R in vivo in a rat model with local hCB₂R overexpression.

Conclusions

[¹¹C]NE40 shows favorable characteristics as radioligand for in vivo visualization of the CB₂R and is a promising candidate for hCB₂R PET imaging.