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 [11C]evobrutinib using a base‐aided palladium‐NiXantphos‐mediated 11C‐carbonylation reaction. [11C]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 [11C]evobrutinib in HT‐29 colorectal cancer mouse xenograft tissues (51.1 ± 7.1%). However, in vivo PET/computed tomography (CT) imaging with [11C]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, [11C]evobrutinib failed to visualize either SARS‐CoV‐2 pseudovirus infection or LPS‐induced injury in mouse models. In conclusion, [11C]evobrutinib was successfully synthesized by 11C‐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.