Cellular metabolic responses of PET radiotracers to 188Re radiation in an MCF7 cell line containing dominant-negative mutant p53
| Autor: | Chang Woon Choi, Soon Hyuk Ahn, Sang Moo Lim, Gi Jeong Cheon, Su Jae Lee, Hye Kyung Chung, Tae Sup Lee, Jung A. Choi |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Cell Survival Cells Blotting Western Cell Apoptosis Biology Transfection Flow cytometry chemistry.chemical_compound Fluorodeoxyglucose F18 Cell Line Tumor Hexokinase medicine Humans Radiology Nuclear Medicine and imaging Viability assay Amino Acids Radioisotopes medicine.diagnostic_test DNA Flow Cytometry Genes p53 Molecular biology Beta Particles Glucose Rhenium medicine.anatomical_structure chemistry Biochemistry Cell culture Positron-Emission Tomography Cancer cell Molecular Medicine Radiopharmaceuticals |
| Zdroj: | Nuclear Medicine and Biology. 34:425-432 |
| ISSN: | 0969-8051 |
| DOI: | 10.1016/j.nucmedbio.2007.01.011 |
| Popis: | We investigated the relations between the cell uptakes of metabolic radiotracers and β-radiation pretreatment using a dominant mutant p53 (p53mt) cell line to evaluate the effects of p53 genes on 18 F labeled positron emission tomography (PET) radiotracer uptakes. Methods pCMV-Neo-Bam (control), which contains a neo-resistance marker, and p53 dominant-negative mutant expression constructs were stably transfected into MCF7 cell line. Cells were plated in 24-well plates at 1.0×10 5 cells for 18 h. Rhenium-188 ( 188 Re) (a beta emitter) was added to the medium (3.7, 18.5, 37 MBq) and incubated for 24 h. We performed gamma-counting to determine the cellular uptakes of 2-[ 18 F]fluoro-2-deoxy-d-glucose (FDG), o -(2-[ 18 F]fluoroethyl)-l-tyrosine (FET) and 2′-[ 18 F]fluoro-2′-deoxythymidine (FLT) (370 kBq, 60 min). Cell viabilities were determined by trypan blue staining and flow cytometry. Results p53mt cells showed 1.5–2-fold higher FDG uptake than wild-type p53 cells in basal condition, and the difference of FDG uptake was greater after 188 Re treatment ( P 188 Re dose without a significant difference between p53 statuses. p53mt cells showed lower FLT uptake than wild-type p53 cells in basal condition, and the difference of FLT uptake was greater after 188 Re treatment. By cell viability testing and FACS analysis, p53mt cells showed lower viability and a larger apoptotic fraction (sub-G1) than wild-type p53 cells after 188 Re treatment. Conclusion We speculate that p53 dysfunction increases glucose and decreases thymidine metabolism in cancer cells and that this may be exaggerated by 188 Re β-radiation. Our findings suggest that FDG could reflect tumor viability and malignant potential after 188 Re β-radiation treatment, whereas FLT could be a more useful PET radiotracer for assessing therapeutic response to β-radiation, especially in cancer cells with an altered function of p53. |
| Databáze: | OpenAIRE |
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