Abstract
2′-Deoxy-2′-fluoro-5-methyl-1-ß-D-arabinofuranosyluracil (FMAU), 9-(4-fluoro-3-hydroxy-methyl-butyl)guanine (FHBG) and 9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]-guanine (FHPG) have been evaluated in a human breast cancer model as potential radiotracers for PET imaging of HSV1-tk gene expression. In vitro accumulation of [ 14C]FMAU, [ 18F]FHBG, and [ 18F]FHPG in HSV1-tk-expressing cells was 14- to 16-fold (p < .001), 9- to 13-fold (p < .001), and 2- to 3-fold (p < .05) higher than tk-negative control cells, respectively, between 30 and 240 min. Accumulation of FMAU and FHBG in vector-transduced cells was 10- to 14-fold and 6- to 10-fold higher than wild-type cells, respectively. At 2 hr, uptake of [ 14C]FMAU in tk-positive cells was 6.3-fold and 60-fold higher than [ 18F]FHBG and [ 18F]FHPG, respectively. In vivo, tumor uptake of [ 14C]FMAU in HSV1-tk-expressing cells was 3.7-fold and 5.5-fold (p < .001) higher than tk-negative control cells at 1 and 2 hr, respectively. Tumor uptake of [ 18F]FHBG was 4,2-fold and 12.6-fold higher (p < .001) than tk-negative cells at the same time points. Incorporation of [ 14C]FMAU in tk-positive tumor was 18-fold and 24-fold higher (p < .001) than [ 18F]FHBG at 1 and 2 hr, respectively. Micro-PET images support the biodistribution results and indicate that both [ 18F]FMAU and [ 18F]FHBG are useful for imaging HSV1-tk expression in breast cancer. Although FMAU demonstrates higher total incorporation (%dose/g) in tumor tissue compared with the other tracers, FHBG is superior in terms of specific accumulation in transfected cells at later time points.
Original language | English (US) |
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Pages (from-to) | 76-84 |
Number of pages | 9 |
Journal | Molecular imaging |
Volume | 3 |
Issue number | 2 |
DOIs | |
State | Published - Apr 2004 |
Keywords
- FHBG
- FMAU
- Gene
- HSV1-tk
- PET
ASJC Scopus subject areas
- Biotechnology
- Molecular Medicine
- Biomedical Engineering
- Radiology Nuclear Medicine and imaging
- Condensed Matter Physics