RT Journal Article
SR Electronic
T1 Iodide Kinetics and Dosimetry In Vivo After Transfer of the Human Sodium Iodide Symporter Gene in Rat Thyroid Carcinoma Cells
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 827
OP 833
VO 45
IS 5
A1 Uwe Haberkorn
A1 Petra Beuter
A1 Wolfgang Kübler
A1 Helmut Eskerski
A1 Michael Eisenhut
A1 Ralf Kinscherf
A1 Sabine Zitzmann
A1 Ludwig G. Strauss
A1 Antonia Dimitrakopoulou-Strauss
A1 Annette Altmann
YR 2004
UL http://jnm.snmjournals.org/content/45/5/827.abstract
AB Transfer of the human sodium iodide symporter (hNIS) has been proposed as a new principle of cancer gene therapy. This study evaluates the iodide kinetics and dosimetry of iodide in hNIS-expressing thyroid carcinoma cells under optimized conditions. Methods: Using a bicistronic retroviral vector for the transfer of the hNIS and the hygromycin resistance gene, hNIS-expressing rat thyroid carcinoma cell lines were generated. Afterward, Na125I uptake and efflux were determined in genetically modified and wild-type cells in the presence or absence of modulators of iodide transport. In addition, the 131I distribution in thyroid-ablated nude mice bearing wild-type and genetically modified thyroid carcinomas was monitored after intraperitoneal administration of 131I with and without coadministration of lithium carbonate. Results: hNIS-expressing cell lines accumulated up to 49 times more iodide than did noninfected cells, with a maximal iodide uptake after 30 min of incubation. However, a 90% efflux of the radioactivity occurred 20 min after replacement of the medium. In mice, the hNIS-expressing tumors accumulated up to 23 and 19.5 times more iodide than did the wild-type tumors in lithium-treated and control animals, respectively. However, efflux of the radioactivity was also observed in vivo: After 24 h, hNIS-expressing tumors lost 82.5% and 80.4% of the initial activity. Dosimetric calculations showed that 1,650 MBq of 131I per square meter resulted in 5.4 and 5.2 Gy in hNIS-expressing tumors and 0.24 and 0.26 in wild-type tumors. Conclusion: Transduction of the hNIS gene in rat thyroid carcinoma cells induces iodide transport, which is associated with rapid efflux. Application of 131I in clinically relevant amounts did not result in therapeutically useful absorbed doses in hNIS-expressing tumors in vivo, even under optimized conditions of thyroid ablation and treatment with lithium carbonate.