Evobrutinib is a second-generation, highly selective, irreversible
Bruton's tyrosine kinase (BTK) inhibitor that has shown efficacy in the
autoimmune diseases arthritis and
multiple sclerosis. Its development as a positron emission tomography (PET) radiotracer has potential for in vivo imaging of BTK in various disease models including several
cancers, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), and
lipopolysaccharide (LPS)-induced lung damage. Herein, we report the automated radiosynthesis of [11 C]
evobrutinib using a base-aided
palladium-NiXantphos-mediated 11 C-carbonylation reaction. [11 C]
Evobrutinib was reliably formulated in radiochemical yields of 5.5 ± 1.5% and a molar activity of 34.5 ± 17.3 GBq/μmol (n = 12) with 99% radiochemical purity. Ex vivo autoradiography studies showed high specific binding of [11 C]
evobrutinib in HT-29
colorectal cancer mouse xenograft tissues (51.1 ± 7.1%). However, in vivo PET/computed tomography (CT) imaging with [11 C]
evobrutinib showed minimal visualization of HT-29
colorectal cancer xenografts and only a slight increase in radioactivity accumulation in the associated time-activity curves. In preliminary PET/CT studies, [11 C]
evobrutinib failed to visualize either SARS-CoV-2 pseudovirus
infection or LPS-induced injury in mouse models. In conclusion, [11 C]
evobrutinib was successfully synthesized by 11 C-carbonylation and based on our preliminary studies does not appear to be a promising BTK-targeted PET radiotracer in the
rodent disease models studied herein.