Could Tc-99m-MIBI be used to visualize the apoptotic MCF7 human breast cancer cells?

Defects in key components of apoptotic pathways provide a survival advantag e to cells and have been implicated as important Factors in tumorogenesis. As therapeutic drug-induced apoptosis is a key component in treatment of mo st cancers, alterations in apoptotic pathways may be critical to drug resis tance. The question is: would it be possible to distinguish apoptotic cells and resistant cells with a same radiotracer? In this study, we investigate d the ability of sodium phenylacetate (NaPa), a natural cytostatic proapopt otic metabolite. to induce apoptosis in MCF7 human breast cancer cells. The n, we tested the Tc-99m-MIBI accumulation in these apoptotic cells. Annexin V-FITC was used to identify apoptotic cells by flow cytometry. Ours result s demonstrated that a 72 hr treatment of MCF7 cells with 40 mM NaPa induced apoptosis in 60% of cells. In a parallel way; Tc-99m-MIBI accumulation in NaPa treated cells decreased for concentrations higher than 20 mM NaPa. Thu s, Tc-99m-MIBI accumulation decreased correlatively with the increasing per centage of apoptotic cells obtained by treatment of MCF7 cells with NaPa. T hese data demonstrate that NaPa induced apoptosis in MCF7 cells and that Tc -99m-MIBI is a negative tracer of apoptosis: the more MCF7 cells were engag ed in the apoptotic pathway, the more Tc-99m-MIBI accumulation decreased in these MCF7 apoptotic cells.