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- Title
Enhanced iodide transport after transfer of the human sodium iodide symporter gene is associated with lack of retention and low absorbed dose.
- Authors
Haberkorn, U; Kinscherf, R; Kissel, M; Kubler, W; Mahmut, M; Sieger, S; Eisenhut, M; Peschke, P; Altmann, A
- Abstract
Transfer of the sodium iodide symporter (hNIS) has been proposed as a new principle of cancer gene therapy. Using clinically relevant doses of 131I for the treatment of NIS-expressing prostate carcinoma cells, we investigated the kinetics and the absorbed doses obtained in these tumors. hNIS-expressing cell lines accumulated up to 200 times more iodide when compared to wild-type cells. However, a rapid efflux of the radioactivity (80%) occurred during the first 20?min after replacement of the medium. In rats, the hNIS-expressing tumors accumulated up to 20 times more iodide when compared to contralateral transplanted wild-type tumors. After 24?h and doses of 550, 1200 or 2400?MBq/m2 hNIS-expressing tumors lost 89, 89 and 91% of the initial activity, respectively. Dosimetric calculations showed that 1200?MBq/m2 resulted in 3±0.5?Gy (wild-type tumor 0.15±0.1?Gy) and 2400?MBq/m2 resulted in 3.1±0.9?Gy (wild-type tumor 0.26±0.02?Gy). Although transduction of the hNIS gene induces iodide transport in rat prostate adenocarcinoma a rapid efflux occurs, which leads to a low absorbed dose in genetically modified tumors. With regard to a therapeutic application additional conditions need to be defined leading to iodide trapping.Gene Therapy (2003) 10, 774-780. doi:10.1038/sj.gt.3301943
- Subjects
IODIDES; GENETIC transformation; ADENOCARCINOMA
- Publication
Gene Therapy, 2003, Vol 10, Issue 9, p774
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301943