Radiofluorinated histamine H₃ receptor antagonist as a potential probe for in vivo PET imaging: radiosynthesis and pharmacological evaluation.

The histamine H3 receptor (H3R) plays a role in cognition and memory processes and is implicated in different neurological disorders, including Alzheimer’s disease, schizophrenia, and narcolepsy. In vivo studies of the H3R occupancy using a radiolabeled PET tracer would be very useful for CNS drug discovery and development. We report here the radiosynthesis, in vitro and in vivo evaluation of a novel 18F-labeled high-affinity H3R antagonist 18F-ST889. The radiosynthesis was accomplished via nucleophilic substitution of the mesylate leaving group with a radiochemical yield of 8–20%, radiochemical purity >99%, and specific radioactivity >65GBq/μmol. 18F-ST889 exhibited high in vivo stability and rather low lipophilicity (logD7.4=0.35±0.09). In vitro autoradiography showed specific binding in H3R-rich brain regions such as striatum and cortex. However, in vivo PET imaging of the rat brain with 18F-ST889 was not successful. Possible reasons are discussed.