Comparison of cellular metabolic responses of (18)F-FDG according to the effect of beta-irradiation in p53 wild and deleted cell lines.
OBJECTIVE
The tumor suppressor gene, p53, plays a pivotal role for cell survival and apoptosis, which could cause different responses to therapeutic agents. Rhenium-188 ((188)Re) decays with the emission of a beta-particle with high energy and is expected to be an important candidate of radiotherapy. We investigated the cellular response of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake and the effect of p53 according to beta-irradiation by (188)Re.


METHODS
The HCT116 human colon adenocarcinoma cell lines, containing a wild-type p53 (p53(+/+)) and a p53-deleted derivative (p53(-/-)), were gifts from Dr. Bert Vogelstein (Johns Hopkins University, Baltimore, MD). Cells were plated in 24-well plates at 1.0 x 10(5) cells, then (188)Re perrhenate was added and incubated for 24 hours. After irradiation, we performed a cellular uptake assay of (18)F-FDG (370 kBq, 60 minutes). We assayed the hexokinase, cell viability, and cell cycle.


RESULTS
p53-deleted HCT116 cells showed a higher (18)F-FDG uptake and increased hexokinase activity after (188)Re treatment. p53-deleted cells showed a higher G2/M (Gap2/Mitosis) arrest in a relatively low dose of beta-irradiation. However, cell viability was not different, according to the p53 status, after (188)Re treatment.


CONCLUSIONS
Therefore, p53 seemed to have a significant role in cellular glucose metabolism and G2/M checkpoint, according to beta-irradiation, and could cause a different therapeutic response of (18)F-FDG uptake in cancer cells.
Chung
Hye-Kyung
HK
Laboratory of Nuclear Medicine Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Cheon
Gi Jeong
GJ
Choi
Chang Woon
CW
Kim
Min-Jung
MJ
Lee
Su-Jae
SJ
Lim
Sang Moo
SM
D001610:Beta Particles; D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism / Q000493:pharmacokinetics*; D005720:Gamma Rays; D017353:Gene Deletion; D045325:HCT116 Cells; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D008660:Metabolism / Q000528:radiation effects; D011868:Radioisotopes; D012211:Rhenium / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D011868:Radioisotopes; D016159:Tumor Suppressor Protein p53; D019788:Fluorodeoxyglucose F18; D012211:Rhenium; D006593:Hexokinase