Synthesis of 4-([¹⁸F]fluoromethyl)-2-chlorophenylisothiocyanate: A novel bifunctional ¹⁸F-labelling agent

The one-step radiosynthesis of 4-([¹⁸F]fluoromethyl)-2-chlorophenylisothiocyanate ¹⁸F-7 as a novel bifunctional ¹⁸F-labelling agent is described. Optimised reaction conditions in a remotely controlled synthesis module gave isothiocyanate ¹⁸F-7 in radiochemical yields of 45 % (decay-corrected) within 40 min and high radiochemical purity of > 95 % after solid-phase-extraction. Coupling of compound ¹⁸F-7 with the primary amine benzylamine as a model reaction afforded the corresponding ((4-[¹⁸F]fluoromethyl)-2-chloro-phenyl)-benzyl thiourea ¹⁸F-8 in a high radiochemical yield of > 90 %. Stability studies of thiourea ¹⁸F-8 in terms of radiodefluorination showed appreciable buffer stability at pH 7.4, whereas significant radiodefluorination was observed when ¹⁸F-8 was incubated in buffers af pH 3.6 and pH 9.4. Preliminary dynamic PET studies with thiourea ¹⁸F-8 in male Wistar rats showed high bone accumulation, indicative of high in vivo radiodefluorination.