[⁷⁶Br]BMK‐I‐152, a non‐peptide analogue for PET imaging of corticotropin‐releasing hormone type 1 receptor (CRHR1)

Abstract The study of corticotropin‐releasing hormone is of significant interest in mental health. We have developed a radiobromination procedure for the preparation of [ 76 Br]BMK‐I‐152, a high‐affinity corticotropin‐releasing hormone type 1 receptor antagonist. The radiobromination procedure resulted in the formation of two radiobrominated products from the same trialkyltin precursor. Utilizing the results of several reaction conditions and the chromatographic and mass spectral data obtained from Waters Acquity and Q‐TOF, we determined that both 3‐bromo and 4‐bromo isomers could be obtained. The authentic sample of the 3‐bromo isomer was prepared to confirm the identity of a previously unknown radioactive side product; affinity assays revealed that the 4‐bromo isomer had ∼70 times higher affinity than that of the 3‐bromo compound. By manipulation of reaction conditions, the individual products could be selected. Under no‐carrier‐added conditions at room temperature in aqueous acetonitrile, the major radioactive product (>80%) was identified as the 3‐[ 76 Br]bromo‐4‐tributylstannyl analogue of BMK‐I‐152. The 4‐[ 76 Br]bromo isomer accounted for less than 1% of the total activity. The 3‐[ 76 Br]bromo BMK‐I‐152 could be obtained by treating this intermediate with trifluoroacetic acid to effect removal of the trialkyltin. If the radiobromination was conducted after first evaporating the water from the aqueous ammonium hydroxide solution of [ 76 Br]bromide, the desired 4‐[ 76 Br]bromo isomer was obtained with a 58% radiochemical yield. Copyright © 2009 John Wiley & Sons, Ltd.