Autotaxin (ATX) is a secreted phosphodiesterase that has been implicated in a remarkably wide array of pathologies, especially in fibrosis and cancer. While ATX inhibitors have entered the clinical arena, a validated probe for positron emission tomography (PET) is currently lacking. With the aim to develop a suitable ATX-targeted PET radioligand, we have synthesized a focused library of fluorinated imidazo[1,2-a]pyridine derivatives, determined their inhibition constants, and confirmed their binding mode by crystallographic analysis. Based on their promising in vitro properties, compounds 9c, 9f, 9h, and 9j were radiofluorinated. Also, a deuterated analog of [F-18]9j, designated as [F-18]ATX-1905 ([F-18]20), was designed and proved to be highly stable against in vivo radiodefluorination compared with [F-18]9c, [F-18]9f, [F-18]9h, and [F-18]9j. These results along with in vitro and in vivo studies toward ATX in a mouse model of LPS-induced liver injury suggest that [F-18]ATX-1905 is a suitable PET probe for the non-invasive quantification of ATX.