The sequential syntheses of [76Br]FBAU 3′,5′-dibenzoate and [76Br]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, Br-76 was produced using the As-75 (He-3, 2n) Br-76 reaction. We then recovered Br-76 from the target in the form of [Br-76]NH4Br with a yield of 60 +/- 12% (n = 32). Peracetic acid was used as the oxidant for electrophilic bromodestannylation to prepare [Br-76]FBAU 3 ' ,5 ' -dibenzoate (71.2 +/- 12.1%, RCY) and a basic hydrolysis of the dibenzoate then yielded [Br-76]FBAU. The yield of the hydrolysis reaction was 53.1 +/- 9.2% when heated at 100 degreesC for 15 min or quantitative (decay corrected) when left at room temperature overnight. The sequential synthesis of [Br-76]FBAU 3 ' ,5 ' -dibenzoate and [Br-76]FBAU allowed us to perform a side-by-side comparison of their metabolic stabilities. While [Br-76]FBAU 3 ' ,5 ' -dibenzoate was hydrolyzed to [Br-76]FBAU within 10 minutes by hepatocyte at 37 degreesC, [Br-76]FBAU was stable and no [Br-76]Br- was released from either radiopharmaceutical. Both compounds are potential proliferation markers for PET. Copyright (C) 2001 John Wiley & Sons, Ltd.