Radiosynthesis of [11C]Ibrutinib via Pd-Mediated [11C]CO Carbonylation: Preliminary PET Imaging in Experimental Autoimmune Encephalomyelitis Mice

被引：8

作者：

Lindberg, Anton ^{[1
,2
]}

Boyle, Amanda J. ^{[1
,2
]}

Tong, Junchao ^{[1
,2
]}

Harkness, Michael B. ^{[1
,2
]}

Garcia, Armando ^{[1
,2
]}

Tran, Tritin ^{[3
]}

Zhai, Dongxu ^{[2
]}

Liu, Fang ^{[2
,4
,5
]}

Donnelly, David J. ^{[3
]}

Vasdev, Neil ^{[1
,2
,4
]}

机构：

[1] Ctr Addict & Mental Hlth, Azrieli Ctr Neuroradiochem, Toronto, ON, Canada

[2] Campbell Family Mental Hlth Res Inst, Brain Hlth Imaging Ctr, Ctr Addict & Mental Hlth, Toronto, ON, Canada

[3] Bristol Myers Squibb Res & Dev, New York, NJ USA

[4] Univ Toronto, Dept Psychiat, Toronto, ON, Canada

[5] Univ Toronto, Dept Physiol, Toronto, ON, Canada

来源：

FRONTIERS IN NUCLEAR MEDICINE | 2021年 / 1卷

基金：

加拿大创新基金会;

关键词：

ibrutinib; multiple sclerosis; positron emission tomography; carbon-11; carbon monoxide; LABELING CHEMISTRY; MONOXIDE;

D O I：

10.3389/fnume.2021.772289

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Ibrutinib is a first-generation Bruton's tyrosine kinase (BTK) inhibitor that has shown efficacy in autoimmune diseases and has consequently been developed as a positron emission tomography (PET) radiotracer. Herein, we report the automated radiosynthesis of [C-11]ibrutinib through C-11-carbonylation of the acrylamide functional group, by reaction of the secondary amine precursor with [C-11]CO, iodoethylene, and palladium-NiXantphos. [C-11]Ibrutinib was reliably formulated in radiochemical yields of 5.4% +/- 2.5% (non-decay corrected; n = 9, relative to starting [C-11]CO2), radiochemical purity >99%, and molar activity of 58.8 +/- 30.8 GBq/mu mol (1.55 +/- 0.83 Ci/mu mol). Preliminary PET/magnetic resonance imaging with [C-11]ibrutinib in experimental autoimmune encephalomyelitis (EAE) mice showed a 49% higher radioactivity accumulation in the spinal cord of mice with EAE scores of 2.5 vs. sham mice.

引用

页数：7

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