Could 99mTc-MIBI be used to visualize the apoptotic MCF7 human breast cancer cells?
Defects in key components of apoptotic pathways provide a survival advantage to cells and have been implicated as important factors in tumorogenesis. As therapeutic drug-induced apoptosis is a key component in treatment of most cancers, alterations in apoptotic pathways may be critical to drug resistance. The question is: would it be possible to distinguish apoptotic cells and resistant cells with a same radiotracer? In this study, we investigated the ability of sodium phenylacetate (NaPa), a natural cytostatic proapoptotic metabolite, to induce apoptosis in MCF7 human breast cancer cells. Then, we tested the 99mTc-MIBI accumulation in these apoptotic cells. Annexin V-FITC was used to identify apoptotic cells by flow cytometry. Ours results demonstrated that a 72 hr treatment of MCF7 cells with 40 mM NaPa induced apoptosis in 60% of cells. In a parallel way, 99mTc-MIBI accumulation in NaPa treated cells decreased for concentrations higher than 20 mM NaPa. Thus, 99mTc-MIBI accumulation decreased correlatively with the increasing percentage of apoptotic cells obtained by treatment of MCF7 cells with NaPa. These data demonstrate that NaPa induced apoptosis in MCF7 cells and that 99mTc-MIBI is a negative tracer of apoptosis: the more MCF7 cells were engaged in the apoptotic pathway, the more 99mTc-MIBI accumulation decreased in these MCF7 apoptotic cells.
Vergote
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J
Department of Nuclear Medicine, Avicenne Hospital, Bobigny, France. jean-luc.moretti@avc.ap-hop-paris.fr
Di Benedetto
M
M
Moretti
J L
JL
Azaloux
H
H
Kouyoumdjian
J C
JC
Kraemer
M
M
Crepin
M
M
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006801:Humans; D010648:Phenylacetates / Q000494:pharmacology; D011877:Radionuclide Imaging / Q000379:methods*; D017256:Technetium Tc 99m Sestamibi / Q000378:metabolism; D014407:Tumor Cells, Cultured
D010648:Phenylacetates; D004247:DNA; D017256:Technetium Tc 99m Sestamibi; C025136:phenylacetic acid