Enhanced iodide transport after transfer of the human sodium iodide symporter gene is associated with lack of retention and low absorbed dose
| Autor: | Ralf Kinscherf, M Kissel, M Eisenhut, Annette Altmann, S Sieger, W Kübler, M Mahmut, Peter Peschke, Uwe Haberkorn |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Genetic enhancement Genetic Vectors Biology Adenocarcinoma Absorption Iodine Radioisotopes Sodium-Iodide Symporter Gene Transduction Genetic Internal medicine Genetics medicine Tumor Cells Cultured Animals Humans Iodide transport Molecular Biology Symporters digestive oral and skin physiology Prostatic Neoplasms Biological Transport Rats Inbred Strains Prostate carcinoma Genetic Therapy Neoplasms Experimental Iodides Molecular biology Immunohistochemistry Rats Endocrinology Retroviridae Absorbed dose Molecular Medicine |
| Zdroj: | Gene therapy. 10(9) |
| ISSN: | 0969-7128 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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