The sequential syntheses of [ 76 Br]FBAU 3′,5′‐dibenzoate and [ 76 Br]FBAU

Thymidine analogs labeled with positron emitting radionuclides are potential proliferation markers for positron emission tomography (PET). Bromine‐76 (T 1/2 =16.2 h) is our choice of radionuclide, because it allows for maximal DNA incorporation of the tracer. Following the literature descriptions, 76 Br was produced using the 75 As ( 3 He, 2n) 76 Br reaction. We then recovered 76 Br from the target in the form of [ 76 Br]NH 4 Br with a yield of 60±12% ( n =32). Peracetic acid was used as the oxidant for electrophilic bromodestannylation to prepare [ 76 Br]FBAU 3′,5′‐dibenzoate (71.2±12.1%, RCY) and a basic hydrolysis of the dibenzoate then yielded [ 76 Br]FBAU. The yield of the hydrolysis reaction was 53.1±9.2% when heated at 100°C for 15 min or quantitative (decay corrected) when left at room temperature overnight. The sequential synthesis of [ 76 Br]FBAU 3′,5′‐dibenzoate and [ 76 Br]FBAU allowed us to perform a side‐by‐side comparison of their metabolic stabilities. While [ 76 Br]FBAU 3′,5′‐dibenzoate was hydrolyzed to [ 76 Br]FBAU within 10 minutes by hepatocyte at 37°C, [ 76 Br]FBAU was stable and no [ 76 Br]Br − was released from either radiopharmaceutical. Both compounds are potential proliferation markers for PET. Copyright © 2001 John Wiley & Sons, Ltd.