(18)F-labeled rhodamines as potential myocardial perfusion agents: comparison of pharmacokinetic properties of several rhodamines.
(18)F-labeled rhodamines as potential myocardial perfusion agents: comparison of pharmacokinetic properties of several rhodamines.
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DOI：
10.1016/j.nucmedbio.2015.06.008
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发表时间：
2015-10
影响因子：
3.1
通讯作者：
Packard AB
中科院分区：
文献类型：
--
作者：
Bartholomä MD;Zhang S;Akurathi V;Pacak CA;Dunning P;Fahey FH;Cowan DB;Treves ST;Packard AB
我们最近报道了罗丹明B的[18 F]氟二甘醇酯作为心肌灌注成像（MPI）的潜在正电子发射断层扫描（PET）示踪剂的发展。该化合物是通过优化罗丹明B核心上的酯部分而开发的，并且发现其药代动力学性质上级原型乙酯。本研究的目的是优化罗丹明核心，同时保留氟代二甘醇酯辅基。一系列不同的罗丹明核心（罗丹明6G，罗丹明101，和四甲基罗丹明）使用相应的罗丹明内酯作为前体和[18 F]氟二甘醇酯作为辅基用18 F标记。通过半制备HPLC纯化化合物，并测定其在大鼠体内的生物分布。此外，在分离的大鼠心肌细胞中评价化合物的摄取。与不同辅基的情况一样，我们发现罗丹明核心对这一系列化合物的体外和体内性质具有显着影响。在迄今评价的罗丹明中，18 F标记的罗丹明6G的二甘醇酯的药理学性质上级于18 F标记的罗丹明B、罗丹明101和四甲基罗丹明的二甘醇酯。与18 F标记的罗丹明B一样，观察到[18 F]罗丹明6 G定位于分离的大鼠心肌细胞的线粒体中。基于这些结果，18F标记的罗丹明6G二甘醇酯是迄今为止已评估的最有前途的潜在PET MPI放射性药物，我们现在正准备用这种化合物进行首次人体临床研究。
We recently reported the development of the [18F]fluorodiethylene glycol ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging (MPI). This compound was developed by optimizing the ester moiety on the rhodamine B core, and its pharmacokinetic properties were found to be superior to those of the prototype ethyl ester. The goal of the present study was to optimize the rhodamine core while retaining the fluorodiethyleneglycol ester prosthetic group. A series of different rhodamine cores (rhodamine 6G, rhodamine 101, and tetramethylrhodamine) were labeled with 18F using the corresponding rhodamine lactones as the precursors and [18F]fluorodiethylene glycol ester as the prosthetic group. The compounds were purified by semipreparative HPLC, and their biodistribution was measured in rats. Additionally, the uptake of the compounds was evaluated in isolated rat cardiomyocytes. As was the case with the different prosthetic groups, we found that the rhodamine core has a significant effect on the in vitro and in vivo properties of this series of compounds. Of the rhodamines evaluated to date, the pharmacologic properties of the 18F-labeled diethylene glycol ester of rhodamine 6G are superior to those of the 18F-labeled diethylene glycol esters of rhodamine B, rhodamine 101, and tetramethylrhodamine. As with 18F-labeled rhodamine B, [18F]rhodamine 6G was observed to localize in the mitochondria of isolated rat cardiomyocytes. Based on these results, the 18F-labeled diethylene glycol ester of rhodamine 6G is the most promising potential PET MPI radiopharmaceutical of those that have been evaluated to date, and we are now preparing to carry out first-in-human clinical studies with this compound.