AUTHOR=Lindberg Anton , Boyle Amanda J. , Tong Junchao , Harkness Michael B. , Garcia Armando , Tran Tritin , Zhai Dongxu , Liu Fang , Donnelly David J. , Vasdev Neil 

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

JOURNAL=Frontiers in Nuclear Medicine

VOLUME=1

YEAR=2021

URL=https://www.frontiersin.org/journals/nuclear-medicine/articles/10.3389/fnume.2021.772289

DOI=10.3389/fnume.2021.772289

ISSN=2673-8880

ABSTRACT=<p>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 [<sup>11</sup>C]ibrutinib through <sup>11</sup>C-carbonylation of the acrylamide functional group, by reaction of the secondary amine precursor with [<sup>11</sup>C]CO, iodoethylene, and palladium–NiXantphos. [<sup>11</sup>C]Ibrutinib was reliably formulated in radiochemical yields of 5.4% ± 2.5% (non-decay corrected; <italic>n</italic> = 9, relative to starting [<sup>11</sup>C]CO<sub>2</sub>), radiochemical purity &gt;99%, and molar activity of 58.8 ± 30.8 GBq/μmol (1.55 ± 0.83 Ci/μmol). Preliminary PET/magnetic resonance imaging with [<sup>11</sup>C]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.</p>