[F-18]-Labeled Positron Emission Tomography Ligand For The Histamine H4 Receptor

We synthesized 5-[F-18]-fluoro-1H-indol-2-yl)(4-methyl-1-piperazinyl)methanone ([F-18]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/mu mol (n = 3). [F-18]5 was stable in rat plasma for at least 4 h and was evaluated by mu PET imaging and biodistribution using a unilateral quinolinic acid rat model of neuroinflammation. The time-activity curve showed that [F-18]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 [F-18]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, [F-18]5 does not appear suitable to image in vivo the receptor by PET.