Synthesis of 18F-radiolabeled diphenyl gallium dithiosemicarbazone using a novel halogen exchange method and in vivo biodistribution

F-radiolabeled diphenyl gallium thiosemicarbazone was prepared by [ F] fluoride exchange of a nitrato anion under mild conditions. The diphenyl gallium thiosemicarbazone chloride is easily prepared in gram quantities and can be used at room temperature in the presence of oxygen. The corresponding nitrate complex is prepared using silver nitrate in methanol solvent and can be stored under nitrogen for weeks before radiolabeling. The biodistribution of this new tracer was studied in mice using Positron Emission Tomography (PET)

Radiolabeling of protected tryptophan with [18F]fluoromethyl tosylate: Formation of [18F]fluoromethyl ester of tryptophan instead of 1-N-[18F]fluoromethyl tryptophan methylester

The reaction of [F]fluoromethyl tosylate with methyl(tert-butoxycarbonyl)-l-tryptophanate results in formation the O-alkylated ester of the tryptophan instead of alkylation of the indole nitrogen of tryptophan as initially anticipated. Treatment of protected tryptophan with NaH in dimethyl formamide (DMF) along with [F]fluoromethyl tosylate at 130°C results in the formation of [F]fluoromethyl(tert-butoxycarbonyl)-l-tryptophanate. Preferential formation of the O-alkylated product is postulated to be due to the hydrolysis of the ester. Confirmation of the O-alkylation was obtained by synthesizing the [F]fluoromethyl(tert-butoxycarbonyl)-l-tryptophanate insitu and examining its NMR characteristics using multiple NMR techniques. Similar results were also obtained when reacting Boc-tryptophan-N-carboxyanhydride precursor with fluoromethyl tosylate