Development of a fast robust derivatization method of an extremely polar PET radiopharmaceutical: a critical aspect for starting a clinical trial

Fluorine-18 labeled (2S,4S)-2-[18F]fluoro-4-(phosphonomethyl)pentanedioic acid (BAY 1075553) has been identified as a prostate specific membrane antigen inhibitor ligand and is being investigated in clinical PET studies for its application in the diagnosis and staging of prostate cancer. To facilitate its transfer to the clinics, it was imperative to develop sensitive analytical methods to characterize the final product with regard to chemical identity, specific activity, and ratio of stereoisomers. This Letter reports on a new rapid quantitative derivatization method for converting an aliquot of the final aqueous formulated product (concentration <10−6 M) into a compound suitable for chiral HPLC analysis to determine the ratio of stereoisomers. This novel analytical method was critical for allowing BAY 1075553 to enter the clinical setting.