Enhanced iodide transport after transfer of the human sodium iodide symporter gene is associated with lack of retention and low absorbed dose

• Verfasst von: Haberkorn, Uwe [VerfasserIn]
• Verfasst von: Kinscherf, Ralf [VerfasserIn]
• Verfasst von: Kübler, Wolfgang [VerfasserIn]
• Verfasst von: Eisenhut, Michael [VerfasserIn]
• Verfasst von: Altmann, Annette [VerfasserIn]
• Titel: Enhanced iodide transport after transfer of the human sodium iodide symporter gene is associated with lack of retention and low absorbed dose
• Verf.angabe: U Haberkorn, R Kinscherf, M Kissel, W Kübler, M Mahmut, S Sieger, M Eisenhut, P Peschke, and A Altmann
• Jahr: 2003
• Umfang: 7 S.
• Fussnoten: Gesehen am 19.10.2017
• Titel Quelle: Enthalten in: Gene therapy
• Ort Quelle: London : Nature Publ. Group, 1997
• Jahr Quelle: 2003
• Band/Heft Quelle: 10(2003), 9, Seite 774-780
• ISSN Quelle: 1476-5462
• DOI: doi:10.1038/sj.gt.3301943
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: gene therapy
• Sach-SW: human sodium iodide transporter
• Sach-SW: prostate carcinoma
• K10plus-PPN: 1564597903

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 30.5 Gy (wild-type tumor 0.150.1 Gy) and 2400 MBq/m2 resulted in 3.10.9 Gy (wild-type tumor 0.260.02 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.