Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

There is considerable interest in developing an F-18-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with Tc-99m-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an F-18-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like Tc-98m-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether F-18-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the F-18-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2'-[F-18]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [F-18]fluoroethyltosylate in acetonitrile at 165 degrees C for 30 min using [F-18]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K2CO3, and [F-18]NaF in acetonitrile for 10 min at 90 degrees C. The product was purified by semi-preparative HPLC to produce the 2'-[F-18]fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/mu mol an isolated decay corrected yield of 35%, and a total synthesis time of 90 min. (C) 2009 Elsevier Ltd. All rights reserved.