[¹⁸ F]-labeled positron emission tomography ligand for the histamine H4 receptor

We synthesized 5-[¹⁸ F]-fluoro-1H-indol-2-yl)(4-methyl-1-piperazinyl)methanone ([¹⁸ F]5) via a Suzuki approach starting from a protected pinacol borane precursor followed by acidic hydrolysis of the t-Boc protecting group. The non-optimized radiochemical yield was 5.7 ± 1.35%, radiochemical purity was over 99%, and molar activity was 100.7 ± 34.5 GBq/μmol (n = 3). [¹⁸ F]5 was stable in rat plasma for at least 4 h and was evaluated by μPET imaging and biodistribution using a unilateral quinolinic acid rat model of neuroinflammation. The time-activity curve showed that [¹⁸ F]5 entered the brain immediately after intravenous injection and then left it progressively with a very low level reached from 30 min after injection. The biodistribution study showed no difference in the accumulation of [¹⁸ F]5 between the lesioned and intact side of the brain and between control rats and animals pretreated with a saturating dose of JNJ-7777120 as a specific H4R antagonist. Hence, despite its in vitro nanomolar affinity for H4R, and its ability to cross the blood-brain barrier in rats, [¹⁸ F]5 does not appear suitable to image in vivo the receptor by PET.