Synthesis of an 18F‐fluorobenzoate idarubicin derivative as new potential PET radiotracer to predict chemotherapy resistance

Anthracyclines are among the most widely used antineoplastic agents in current clinical practice. Nevertheless, chemoresistance, which results in failure to eradicate the tumor, is often observed after administration of anthracyclines, and no assay system has yet been found to accurately predict tumor resistance to those antitumor agents. We sought to prepare an F‐18 labeled derivative of idarubicin, a 4‐demethoxy‐daunorubicin analogue, to use in helping to assess physiologic resistance to anthracyclines in vivo. Two different synthetic pathways, which required the preparation of the key intermediate [¹⁸F]fluorobenzoic acid ([¹⁸F]FBA), are advanced to label idarubicin with F‐18 on its primary amine. The first approach yielded the desired [¹⁸F]fluorobenzoate idarubicin derivative in two steps from [¹⁸F]FBA, while the second strategy consisted of a direct acylation of idarubicin by treatment with [¹⁸F]FBA in presence of diethyl cyanophosphonate. Although the first method led to fewer byproducts, it required more time to obtain the HPLC‐purified radiopharmaceutical (100 min vs 90 min) and resulted in lower radiochemical yields (8–25% vs 25–39% decay corrected from starting fluoride). Copyright © 2005 John Wiley & Sons, Ltd.