Source:http://linkedlifedata.com/resource/pubmed/id/14579096
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
|
pubmed:dateCreated |
2003-10-27
|
pubmed:abstractText |
Earlier studies involving comparison of different reporter probes have shown conflicting results between pyrimidine nucleosides [e.g., 2'-fluoro-2'-deoxy-1-beta- d-arabinofuranosyl-5-iodouracil (FIAU)] and acycloguanosine derivatives [e.g., penciclovir (PCV), 9-(4-fluoro-3-hydroxymethylbutyl)guanine (FHBG)]. We hypothesized that this reported discrepancy may be related to how the reporter gene is delivered to the cells-stably transfected vs adenoviral infection. We directly compared the uptake characteristics of [(18)F]FHBG, [(3)H]PCV, and [(14)C]FIAU in cell culture and in vivo using an adenoviral mediated gene transfer model and stably transfected cells. We further compared the uptake of three reporter probes using both HSV1-tk and a mutant HSV1-sr39tk expressing cells to assess the optimal reporter probe/reporter gene combination. [(14)C]FIAU accumulation was greater than that of [(3)H]PCV and [(18)F]FHBG in control cells and in HSV1-tk stably transfected cells ( P<0.001). After infection of C6 cells with AdCMV- HSV1-tk (1.5x10(8) pfu), [(18)F]FHBG and [(3)H]PCV accumulation was significantly greater than that of [(14)C]FIAU ( P<0.01). [(18)F]FHBG and [(3)H]PCV accumulated to a significantly greater extent than [(14)C]FIAU in C6-stb-sr39tk+ and AdCMV- HSV1-sr39tk infected C6 cells ( P<0.001). Results from the nude mice supported the results in cell culture. [(14)C]FIAU led to significantly higher %ID/g in C6-stb-tk+ xenografts than [(18)F]FHBG ( P<0.05); however, compared with [(14)C]FIAU, [(18)F]FHBG led to as high %ID/g in HSV1-tk expressing hepatocytes and to significantly greater %ID/g in C6-stb-sr39tk+ xenografts and HSV1-sr39tk expressing hepatocytes. Dynamic sequential images showed that [(18)F]FHBG was well retained in HSV1-sr39tk expressing cells (C6-stb-sr39tk+) for at least 4 h after injection, while it was rapidly cleared from HSV1-tk expressing cells (MH3924A-stb-tk+). [(14)C]FIAU accumulated in HSV1-tk stably expressing cells to a greater extent than either [(3)H]PCV or [(18)F]FHBG. However, the accumulation of [(3)H]PCV and [(18)F]FHBG in adenoviral infected C6 cells or hepatocytes was equivalent to or greater than that of [(14)C]FIAU. These results may be due to intracellular biochemical changes (e.g., thymidine) when cells are infected with adenovirus. For adenoviral studies, the [(18)F]FHBG/ HSV1-sr39tk combination was shown to be more sensitive than the [(14)C]FIAU/ HSV1-tk combination HSV1-tk.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/9-(4-fluoro-3-hydroxymethylbutyl)gua...,
http://linkedlifedata.com/resource/pubmed/chemical/Arabinofuranosyluracil,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine,
http://linkedlifedata.com/resource/pubmed/chemical/MON1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Radiopharmaceuticals,
http://linkedlifedata.com/resource/pubmed/chemical/fialuridine
|
pubmed:status |
MEDLINE
|
pubmed:month |
Nov
|
pubmed:issn |
1619-7070
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
30
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1547-60
|
pubmed:dateRevised |
2007-11-14
|
pubmed:meshHeading |
pubmed-meshheading:14579096-Adenoviridae Infections,
pubmed-meshheading:14579096-Animals,
pubmed-meshheading:14579096-Arabinofuranosyluracil,
pubmed-meshheading:14579096-Cell Line, Tumor,
pubmed-meshheading:14579096-Genes, Reporter,
pubmed-meshheading:14579096-Glioma,
pubmed-meshheading:14579096-Guanine,
pubmed-meshheading:14579096-Male,
pubmed-meshheading:14579096-Metabolic Clearance Rate,
pubmed-meshheading:14579096-Mice,
pubmed-meshheading:14579096-Organ Specificity,
pubmed-meshheading:14579096-Proteins,
pubmed-meshheading:14579096-Radiopharmaceuticals,
pubmed-meshheading:14579096-Rats,
pubmed-meshheading:14579096-Tissue Distribution,
pubmed-meshheading:14579096-Tomography, Emission-Computed,
pubmed-meshheading:14579096-Transfection
|
pubmed:year |
2003
|
pubmed:articleTitle |
Comparison of [18F]FHBG and [14C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection.
|
pubmed:affiliation |
The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095-1770, USA.
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|