Tc-Tetrofosmin (Tc-TF) and Tc-Sestamibi (Tc-MIBI) are SPECT tracers that have been used for brain tumor imaging. Tumor’s multidrug resistance phenotype, namely, P-glycoprotein (p-gp), and the multidrug resistance related proteins (MRPs) expression have been suggested to influence both tracers’ uptake. In the present study we set out to compare Tc-TF and Tc-MIBI uptake in high-grade glioma cell lines and to investigate the influence of gliomas p-gp expression on both tracers’ uptake. We used four glioma cell lines (U251MG, A172, U87MG, and T98G). The expression of p-gp protein was evaluated by flow cytometry. Twenty μCi (7.4·105？Bq) of Tc-TF and Tc-MIBI were used. The radioactivity in the cellular lysate was measured with a dose calibrator. P-gp was significantly expressed only in the U251MG cell line (). In all gliomas cell lines (U251MG, U87MG, A172, and T98G) the Tc-TF uptake was significantly higher than Tc-sestamibi. The U251MG cell line, in which significant p-gp expression was documented, exhibited the strongest uptake difference. Tc-TF uptake was higher than Tc-MIBI in all studied high-grade glioma cell lines. Thus, Tc-TF may be superior to Tc-MIBI for glioma imaging in vivo. 1. Introduction -Tetrofosmin (-TF) and -sestamibi (-MIBI) are tracers that have been used among others for brain tumor imaging [1, 2]. Both agents have been used for the differentiation of glioma recurrence from treatment induced necrosis [3, 4], neoplastic from nonneoplastic intracerebral hemorrhage [5], assessment of glioma and meningioma aggressiveness and patient’s prognosis [6, 7]. Nevertheless, several studies proposed that -TF might be superior to -MIBI for brain tumor imaging, since the latter is influenced to a greater degree by tumor’s multidrug resistance phenotype (MDR) [8–10]. MDR phenotype is associated with P-glycoprotein (p-gp) and multidrug resistance related proteins (MRPs) expression. These proteins act as membrane-efflux transporters that pump drugs out of the cancer cells and reduce intracellular concentration [11]. Both -TF and -MIBI are substrates of these pumps [8, 9]. In the present study we set out to compare -TF and -MIBI uptake in four high-grade glioma cell lines and the influence of p-gp expression on tracer uptake. 2. Material and Methods 2.1. Cell Lines The human glioma cell lines U251MG and A172 were obtained from Dr. W. K. Alfred Yung (Department of Neuro-Oncology, M.D. Anderson Cancer Center, Houston, TX). U87MG and T98G were obtained from American Type Culture Collection (ATCC; Manassas, VA, USA). They were cultured in Dulbecco’s modified
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