Radiosynthesis of [11C]6-OH-BTA-1 in Different Media and Confirmation of Reaction By-products

Lee, Hak Jeong; Jeong, Jae Min; Lee, Yun Sang; Kim, Hyung Woo; Lee, Eun Kyoung; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul

Abstract

PURPOSE: [11C]6-OH-BTA-1 ([N-methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, 1), a -amyloid imaging agent for the diagnosis of Alzheimer's disease in PET, can be labeled with higher yield by a simple loop method. During the synthesis of [11C]1, we found the formation of by-products in various solvents, e.g., methylethylketone (MEK), cyclohexanone (CHO), diethylketone (DEK), and dimethylformamide (DMF).
MATERIALS AND METHODS
In Automated radiosynthesis module, 1 mg of 4-aminophenyl-6-hydroxybenzothiazole (4) in 100 l of each solvent was reacted with [11C]methyl triflate in HPLC loop at room temperature (RT). The reaction mixture was separated by semi-preparative HPLC. Aliquots eluted at 14.4, 16.3 and 17.6 min were collected and analyzed by analytical HPLC and LC/MS spectrometer.
RESULTS
The labeling efficiencies of [11C]1 were 86.0+/-5.5%, 59.7+/-2.4%, 29.9+/-1.8%, and 7.6+/-0.5% in MEK, CHO, DEK and DMF, respectively. The LC/MS spectra of three products eluted at 14.4, 16.3 and 17.6 mins showed m/z peaks at 257.3 (M+1), 257.3 (M+1) and 271.3 (M+1), respectively, indicating their structures as 1, 2-(4'-aminophenyl)-6-methoxybenzothiazole (2) and by-product (3), respectively. Ratios of labeling efficiencies for the three products ([11C]1:[11C]2:[11C]3) were 86.0+/-5.5%:5.0+/-3.4%:1.5+/-1.3% in MEK, 59.7+/-2.4%:4.7+/-3.2%:1.3+/-0.5% in CHO, 9.9+/-1.8%:2.0+/-0.7%:0.3+/-0.1% in DEK and 7.6+/-0.5%:0.0%:0.0% in DMF, respectively.
CONCLUSION
The labeling efficiency of [11C]1 was the highest when MEK was used as a reaction solvent. As results of mass spectrometry, 1 and 2 were conformed. 3 was presumed.