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

• Published in: Applied radiation and isotopes 2010-01, Vol.68 (1), p.96-100
• Main Authors: Heinrich, Tobias K., Gottumukkala, Vijay, Snay, Erin, Dunning, Patricia, Fahey, Frederic H., Ted Treves, S., Packard, Alan B.
• Format: Article
• Language: English
• Subjects: Animals; Fluorine Radioisotopes - chemistry; Fluorine-18; Isotope Labeling; Mice; Myocardial perfusion imaging; Myocardial Perfusion Imaging - methods; Positron emission tomography; Positron-Emission Tomography - methods; Radiopharmaceuticals - chemical synthesis; Rhodamine B; Rhodamines - chemical synthesis; Rhodamines - pharmacokinetics
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2009.08.013

There is considerable interest in developing an 18F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with 99mTc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an 18F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like 99mTc-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 18F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the 18F-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′-[ 18F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [ 18F]fluoroethyltosylate in acetonitrile at 165 °C for 30 min using [ 18F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K 2CO 3, and [ 18F]NaF in acetonitrile for 10 min at 90 °C. The product was purified by semi-preparative HPLC to produce the 2′-[ 18F]fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/μmol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min.