[carbonyl-¹¹C]4-Fluoro-N-methyl-N-(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([¹¹C]FIMX) is an effective radioligand for PET imaging of metabotropic glutamate receptor 1 (mGluR1) in monkey brain

详细信息    查看全文

• 作者：Jinsoo Hong ; Shuiyu Lu ; Rong Xu ; Jeih-San Liow ; Alicia E. Woock ; Kimberly J. Jenko ; Robert L. Gladding ; Sami S. Zoghbi ; Robert B. Innis ; Victor W. Pike ; ^{pikev@mail.nih.gov" class="auth_mail" title="E-mail the corresponding author}
• 关键词：mGluR1 ; Radioligand ; PET ; Carbon-11 ; Monkey ; Brain
• 刊名：Nuclear Medicine and Biology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：42
• 期：12
• 页码：967-974
• 全文大小：974 K

文摘

Metabotropic glutamate subtype receptor 1 (mGluR1) is implicated in several neuropsychiatric disorders and is a target for drug development. [¹⁸F]FIMX ([¹⁸F]4-fluoro--N-methyl-N--(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide) is an effective radioligand for imaging brain mGluR1 with PET. A similarly effective radioligand with a shorter half-life would usefully allow PET studies of mGluR1 at baseline and after pharmacological or other challenge on the same day. Here we describe the preparation of [¹¹C]FIMX for evaluation in monkey with PET.

Methods

[¹¹C]FIMX was prepared via Pd-promoted carbonylation of 1-fluoro-4-iodobenzene with [¹¹C]carbon monoxide, aminolysis of the [¹¹C]acyl-palladium complex with the requisite Boc-protected amine, and deprotection with HCl in THF. PET scans of [¹¹C]FIMX injected into a monkey were performed at baseline and after preblock of mGluR1 with measurement of the arterial input function.

Results

The radiosynthesis required 42 min and gave [¹¹C]FIMX in about 5% overall decay-corrected radiochemical yield and with a specific activity of about 100 GBq/μmol. PET in rhesus monkey at baseline showed that radioactivity peaked high in receptor-rich cerebellum and much lower in receptor-poor occipital cortex. Radioactivity in cerebellum declined to 32% of peak at 85 min. V_T at baseline appeared stable in all brain regions after 60 min. Under mGluR1 pre-blocked condition, radioactivity uptake in all regions declined more rapidly to a low level. Receptor pre-block reduced V_T from 13.0 to 1.5 in cerebellum and from 2.9 to 1.4 in occipital cortex.

Conclusion

[¹¹C]FIMX is an effective radioligand for imaging mGluR1 in monkey with PET.