Heinrich Tobias K, Gottumukkala Vijay, Snay Erin, Dunning Patricia, Fahey Frederic H, Ted Treves S, Packard Alan B
Division of Nuclear Medicine, Department of Radiology, Children's Hospital Boston, 300 Longwood Ave., Boston, MA 02115, USA.
Appl Radiat Isot. 2010 Jan;68(1):96-100. doi: 10.1016/j.apradiso.2009.08.013. Epub 2009 Aug 28.
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.
开发一种（18）F标记的PET心肌灌注剂引起了人们的极大兴趣。罗丹明染料与最常用的单光子心肌灌注剂（99m）Tc-MIBI具有若干共同特性，这表明（18）F标记的罗丹明染料可能在该应用中有用。除了像（99m）Tc-MIBI一样是亲脂性阳离子外，罗丹明染料已知会在心肌中蓄积，并且是Pgp的底物，Pgp是与MDR1多药耐药性相关的蛋白质。作为确定（18）F标记的罗丹明是否可用作PET心肌灌注剂的第一步，我们的目标是开发合成方法来制备（18）F标记的化合物，以便能够在体内对其进行评估。选择罗丹明B作为合成开发的原型化合物，因为罗丹明B胺部分上的乙基取代基可保护它们免受副反应影响，从而无需引入（并随后去除）保护基团。罗丹明B的2'-[（18）F]氟乙酯是通过将罗丹明B内酯与[（18）F]氟乙基对甲苯磺酸酯在乙腈中于165℃加热30分钟来合成的，使用的[（18）F]氟乙基对甲苯磺酸酯是由乙二醇二对甲苯磺酸酯与穴醚2.2.2、K2CO3和[（18）F]NaF在乙腈中于90℃反应10分钟制备的。产物通过半制备HPLC纯化，以>97%的放射化学纯度得到2'-[（18）F]氟乙酯，比活为1.3GBq/μmol，分离的衰变校正产率为35%，总合成时间为90分钟。
