Radiochemical synthesis, automation, and in vivo biodistribution of 4-[¹⁸F] Fluorobenzyl-Harmine (F-18 FB-Harmine)

Objectives Previous efforts to develop PET imaging probes to study Monoamine oxidase (MAO) primarily focused on developing C-11 labeled compouds such as C-11 deprenyl, C-11 Harmine, and C-11 clorgyline. An F-18 labeled compound will allow for its use at sites without an on-site cyclotron. Herein, we report synthesis of a novel F-18 fluorobenzyl analogue of harmine and our preliminary results from biodistribution studies performed in normal rats.

Methods F-18 FB-Harmine was prepared by reacting 4-[¹⁸F]fluorobenzyl iodide (prepared as described earlier) with Harmine (1 eq) and NaH (1.3 eq) at 110°C for 10 min. The desired product was isolated using a semi-prep HPLC. The synthesis was controlled remotely through an automated PLC unit. Five rats were injected with 20 μCi F-18 FB-Harmine and were sacrificed 60 min post injection. Various tissues were excised, weighed, and counted for radioactivity.

Results The radiochemical synthesis was automated for reliability and safe handling. F-18 FB-Harmine was prepared in 28.8±4.5% RCY with a specific activity of >2000 mCi/μmole and in synthesis time of 150 min. The in vivo biodistribution studies show a rapid clearance of radioactivty primarily via urinary excretion.The F-18 uptake in liver, spleen, lungs, kidney, pancrease, adrenal glands, and muscle was 0.40±0.11, 0.12±0.02, 0.13±0.02, 0.35±0.06, 0.15±0.06, 0.08±0.04, and 0.04±0.01%ID/g tissue, respectively. Uptake in the brain was modest, providing brain to muscle ratio of 1.9±0.27 at 60 min. A low bone uptake (0.05±0.01%ID/g) demonstrated its resistance to in vivo defluorination.

Conclusions Herein, we report a novel F-18 labeled MAO probe i.e. F-18 FB-Harmine for PET imaging. The product was prepared in good RCY and high specific activity, using an automated process. The in vivo biodistribution studies show an overall low F-18 accumulation in most normal organs and a modest uptake in the brain. Additional studies are planned to further elucidate its uptake specificity and retention characteristics