| Cellular metabolic responses of PET radiotracers to (188)Re radiation in an MCF7 cell line containing dominant-negative mutant p53. | |
| | |
MedLine Citation:
|
PMID: 17499732 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
We investigated the relations between the cell uptakes of metabolic radiotracers and beta-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 1.0x10(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<.01). FET uptake increased with (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 beta-radiation. Our findings suggest that FDG could reflect tumor viability and malignant potential after (188)Re beta-radiation treatment, whereas FLT could be a more useful PET radiotracer for assessing therapeutic response to beta-radiation, especially in cancer cells with an altered function of p53. |
| | |
Authors:
|
Gi Jeong Cheon; Hye-Kyung Chung; Jung-A Choi; Su-Jae Lee; Soon-Hyuk Ahn; Tae-Sup Lee; Chang Woon Choi; Sang Moo Lim |
Publication Detail:
|
Type: Journal Article Date: 2007-03-30 |
Journal Detail:
|
Title: Nuclear medicine and biology Volume: 34 ISSN: 0969-8051 ISO Abbreviation: Nucl. Med. Biol. Publication Date: 2007 May |
Date Detail:
|
Created Date: 2007-05-14 Completed Date: 2007-08-13 Revised Date: 2009-11-19 |
Medline Journal Info:
|
Nlm Unique ID: 9304420 Medline TA: Nucl Med Biol Country: England |
Other Details:
|
Languages: eng Pagination: 425-32 Citation Subset: IM |
Affiliation:
|
Laboratory of Nuclear Medicine Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea. larry@kcch.re.kr |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acids
/
biosynthesis Apoptosis / drug effects, radiation effects Beta Particles Blotting, Western Cell Line, Tumor Cell Survival / drug effects, radiation effects Cells / metabolism*, radiation effects* DNA / biosynthesis Flow Cytometry Fluorodeoxyglucose F18 / pharmacokinetics, pharmacology Genes, p53 / genetics* Glucose / biosynthesis Hexokinase / metabolism Humans Positron-Emission Tomography Radioisotopes Radiopharmaceuticals / pharmacokinetics* Rhenium* Transfection |
| Chemical | |
Reg. No./Substance:
|
0/Amino Acids; 0/Radioisotopes; 0/Radiopharmaceuticals; 50-99-7/Glucose; 63503-12-8/Fluorodeoxyglucose F18; 7440-15-5/Rhenium; 9007-49-2/DNA; EC 2.7.1.1/Hexokinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Biodistribution, pharmacokinetics and imaging of (188)Re-BMEDA-labeled pegylated liposomes after int...
Next Document: An automated one-step one-pot [(18)F]FCWAY synthesis: development and minimization of chemical impur...