Cellular metabolic responses of PET radiotracers to 188Re radiation in an MCF7 cell line containing dominant-negative mutant p53

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 18F labeled positron emission tomography (PET) radiotracer uptakes.MethodspCMV-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 1.0×105 cells for 18 h. Rhenium-188 (188Re) (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-[18F]fluoro-2-deoxy-d-glucose (FDG), o-(2-[18F]fluoroethyl)-l-tyrosine (FET) and 2′-[18F]fluoro-2′-deoxythymidine (FLT) (370 kBq, 60 min). Cell viabilities were determined by trypan blue staining and flow cytometry.Resultsp53mt 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 188Re treatment (P<.01). FET uptake increased with 188Re 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 188Re 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 188Re treatment.ConclusionWe speculate that p53 dysfunction increases glucose and decreases thymidine metabolism in cancer cells and that this may be exaggerated by 188Re β-radiation. Our findings suggest that FDG could reflect tumor viability and malignant potential after 188Re 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.