title: Enhanced iodide transport after transfer of the human sodium iodide symporter gene is associated with lack of retention and low absorbed dose.
abstract: Transfer of the sodium iodide symporter (hNIS) has been proposed as a new principle of cancer gene therapy. Using clinically relevant doses of (131)I 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/m(2) hNIS-expressing tumors lost 89, 89 and 91% of the initial activity, respectively. Dosimetric calculations showed that 1200 MBq/m(2) resulted in 3+/-0.5 Gy (wild-type tumor 0.15+/-0.1 Gy) and 2400 MBq/m(2) 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.
authors.affiliation: Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Haberkorn
authors.forename: R
authors.initials: R
authors.lastname: Kinscherf
authors.forename: M
authors.initials: M
authors.lastname: Kissel
authors.forename: W
authors.initials: W
authors.lastname: Kübler
authors.forename: M
authors.initials: M
authors.lastname: Mahmut
authors.forename: S
authors.initials: S
authors.lastname: Sieger
authors.forename: M
authors.initials: M
authors.lastname: Eisenhut
authors.forename: P
authors.initials: P
authors.lastname: Peschke
authors.forename: A
authors.initials: A
authors.lastname: Altmann
mesh_terms: D000042:Absorption; D000230:Adenocarcinoma / Q000378:metabolism / Q000532:radiotherapy*; D000818:Animals; D001692:Biological Transport; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D009374:Neoplasms, Experimental; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D051381:Rats; D011919:Rats, Inbred Strains; D012190:Retroviridae / Q000235:genetics; D027981:Symporters / Q000032:analysis / Q000235:genetics*; D014161:Transduction, Genetic / Q000379:methods; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters
chemical_list: D007454:Iodides; D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters