Biological characterization of F-18-labeled rhodamine B, a potential positron emission tomography perfusion tracer.
Biological characterization of F-18-labeled rhodamine B, a potential positron emission tomography perfusion tracer.
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DOI：
10.1016/j.nucmedbio.2013.07.006
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发表时间：
2013-11
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;He H;Pacak CA;Dunning P;Fahey FH;McGowan FX;Cowan DB;Treves ST;Packard AB
心肌梗死是西方国家的主要死亡原因，正电子发射断层扫描（PET）在心肌梗死的诊断和治疗计划中发挥着越来越重要的作用。然而，缺乏F-18标记的PET心肌灌注示踪剂阻碍了PET在心肌灌注成像（MPI）中的广泛应用。我们最近报道了一种基于F-18标记的罗丹明B的潜在MPI剂。本研究的目的是更完整地定义F-18标记的罗丹明B在心肌梗死动物模型中的摄取和定位的生物学特性，并评估心肌细胞对F-18标记的罗丹明B的摄取。用小动物PET研究了12只永久性结扎左前降支（LAD）的雌性Sprague道利大鼠。给动物注射100-150 µCi F-18标记的罗丹明B二甘醇酯（[18 F]RhoBDEGF），并在结扎前两天成像。结扎后2至10天再次对动物成像。在手术后扫描后，将动物安乐死，将心脏切成1 mm的切片，并通过磷光成像和氯化2，3，5-三苯基四唑（TTC）染色来确定心肌梗死面积。此外，[18 F]RhoBDEGF在分离的大鼠新生心肌细胞的摄取测定通过荧光显微镜。小动物PET显示健康大鼠心肌中[18F]RhoBDEGF的摄取强烈且均匀。左前降支结扎后，在PET图像上观察到了明确的灌注缺损。缺损的大小与梗死面积高度相关，如通过磷光成像和TTC染色离体测定的。在体外，[18 F]RhoBDEGF迅速内化到大鼠心肌细胞中，在60 min孵育时间内内化了约40%的初始活性。荧光显微镜清楚地表明[18 F]RhoBDEGF在大鼠心肌细胞线粒体中的定位。氟-18-标记的罗丹明B二甘醇酯（[18 F]RhoBDEGF）在大鼠梗死模型中提供了极好的图像质量和清晰的心肌梗死描绘。体外研究表明示踪剂定位在心肌细胞的线粒体中。总之，这些结果支持继续评价该示踪剂用于心肌灌注PET评估。
Myocardial infarction is the leading cause of death in western countries, and positron emission tomography (PET) plays an increasing role in the diagnosis and treatment planning for this disease. However, the absence of an F-18-labeled PET myocardial perfusion tracer hampers the widespread use of PET in myocardial perfusion imaging (MPI). We recently reported a potential MPI agent based on F-18-labeled rhodamine B. The goal of this study was to more completely define the biological properties of F-18-labeled rhodamine B with respect to uptake and localization in an animal model of myocardial infarction and to evaluate the uptake F-18-labeled rhodamine B by cardiomyocytes. A total of 12 female Sprague Dawley rats with a permanent ligation of the left anterior descending artery (LAD) were studied with small-animal PET. The animals were injected with 100–150 µCi of F-18-labeled rhodamine B diethylene glycol ester ([18F]RhoBDEGF) and imaged two days before ligation. The animals were imaged again two to ten days post-ligation. After the post-surgery scans, the animals were euthanized and the hearts were sectioned into 1 mm slices and myocardial infarct size was determined by phosphorimaging and 2,3,5-triphenyltetrazolium chloride staining (TTC). In addition, the uptake of [18F]RhoBDEGF in isolated rat neonatal cardiomyocytes was determined by fluorescence microscopy. Small-animal PET showed intense and uniform uptake of [18F]RhoBDEGF throughout the myocardium in healthy rats. After LAD ligation, well defined perfusion defects were observed in the PET images. The defect size was highly correlated with the infarct size as determined ex vivo by phosphorimaging and TTC staining. In vitro, [18F]RhoBDEGF was rapidly internalized into rat cardiomyocytes with ~40 % of the initial activity internalized within the 60 min incubation time. Fluorescence microscopy clearly demonstrated localization of [18F]RhoBDEGF in the mitochondria of rat cardiomyocytes. Fluorine-18-labeled rhodamine B diethylene glycol ester ([18F]RhoBDEGF) provides excellent image quality and clear delineation of myocardial infarcts in a rat infarct model. In vitro studies demonstrate localization of the tracer in the mitochondria of cardiac myocytes. In combination, these results support the continued evaluation of this tracer for the PET assessment of myocardial perfusion.
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影响因子：
5.7
作者：
Higuchi, Takahiro;Bengel, Frank M.
通讯作者：
Bengel, Frank M.
影响因子：
3.3
作者：
Lacerda, SHD;Abraham, B;Indig, GL
通讯作者：
Indig, GL
影响因子：
3.1
作者：
Shoup, Timothy M.;Elmaleh, David R.;Fischman, Alan J.
通讯作者：
Fischman, Alan J.
影响因子：
3.9
作者：
Choi, JY;Kim, SE;Kim, JH
通讯作者：
Kim, JH
影响因子：
1.6
作者：
Heinrich, Tobias K.;Gottumukkala, Vijay;Snay, Erin;Dunning, Patricia;Fahey, Frederic H.;Treves, S. Ted;Packard, Alan B.
通讯作者：
Packard, Alan B.