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Tetramethylrhodamine ethyl ester (TMRE) is a cell-permeant, lipophilic, cationic fluorescent dye widely utilized in biological research as a potentiometric probe to measure mitochondrial membrane potential (ΔΨm). Due to its positive charge, TMRE accumulates within the negatively charged mitochondrial matrix in a Nernstian fashion, allowing for the visualization and quantification of mitochondrial activity via fluorescence microscopy or flow cytometry. In the context of neuro-oncology, TMRE has been investigated as a 'tumor painting' agent for the intraoperative identification of glioblastoma boundaries, leveraging the characteristic mitochondrial hyperpolarization found in many cancer cells. However, preclinical evaluations in intracranial xenograft models have demonstrated that TMRE possesses significant systemic toxicity, which has limited its translation into clinical practice compared to more tolerable rhodamine derivatives like fluoroethylrhodamine ester (RhoFe). Additionally, TMRE exhibits phototoxic properties in cell culture, suggesting potential utility in photodynamic therapy research.
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