Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent.
There is considerable interest in developing an (18)F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with (99m)Tc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an (18)F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like (99m)Tc-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 (18)F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the (18)F-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'-[(18)F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [(18)F]fluoroethyltosylate in acetonitrile at 165 degrees C for 30min using [(18)F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K(2)CO(3), and [(18)F]NaF in acetonitrile for 10min at 90 degrees C. The product was purified by semi-preparative HPLC to produce the 2'-[(18)F]fluoroethylester in >97% radiochemical purity with a specific activity of 1.3GBq/mumol, an isolated decay corrected yield of 35%, and a total synthesis time of 90min.
Heinrich
Tobias K
TK
Division of Nuclear Medicine, Department of Radiology, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA.
Gottumukkala
Vijay
V
Snay
Erin
E
Dunning
Patricia
P
Fahey
Frederic H
FH
Ted Treves
S
S
Packard
Alan B
AB
D000818:Animals; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling; D051379:Mice; D055414:Myocardial Perfusion Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D012235:Rhodamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics
C546839:2'-fluoroethyl rhodamine B; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D012235:Rhodamines; C029773:rhodamine B