Radiosynthesis of [N-methyl-11C]methylene blue

Abstract

We have synthesized the novel radiotracer [N-methyl-11C]methylene blue (MB). 3,7-Bis(dimethylamino)phenothiazine-5-ium chloride (methylene blue) accumulates selectively in melanoma cells [1]. Melanoma is the most serious form of skin cancer. Our aim was to label methylene blue with the short lived positron-emitting 11C isotope (T1/2=20.4 min) in order to use it as an in vivo PET tracer for patients suffering from melanoma and probably other diseases. The radiosynthesis of MB was performed by 11C methylation of Azure B (AB). For this, [11C]methyl triflate was trapped in a reaction vessel containing a solution of AB and potassium carbonate in water. After the solution was stirred at room temperature for 5 min it was transferred on to a cation exchange cartridge which was washed with ethanol and sterile water. Then the cartridge was rinsed with sterile sodium chloride 0.9% w/v solution to provide MB. Radiochemical purity and specific activity of the final solution was determined by HPLC. The preparation of the novel radiotracer [N-methyl-11C]methylene blue was completed in 35 min and resulted in a radiochemical purity greater than 97% and an overall radiochemical yield of 4–6%. We conclude that a fully automated synthesis module for the regular production of [N-methyl-11C]methylene blue has to be constructed.