Effective treatment of pancreatic neuroendocrine tumours transfected with the sodium iodide symporter gene by 186Re-perrhenate in mice.
OBJECTIVE
ReO(4)(-) has similar kinetics regarding the sodium iodide symporter (NIS) to I(-) and TcO(4)(-) in NIS-expressing tissue. We investigated the therapeutic potential of (186)ReO(4)(-) in NIS-transfected neuroendocrine tumour tissue.


METHODS
For experiments, the stably NIS-transfected pancreatic neuroendocrine cancer cell line Bon1C was used. NIS-mediated internalization and externalization experiments in vitro and a biodistribution study in nude mice bearing Bon1C xenografts were performed. A therapy study was also conducted consecutively in nude mice xenografted with Bon1C in which the mice were injected intravenously with Na(186)ReO(4).


RESULTS
In vitro studies showed exponential internalization and efflux kinetics of (186)ReO(4)(-) in the cell line. The biodistribution study showed high uptake of (186)ReO(4)(-) in NIS-expressing tumours. Tumour growth inhibition was significant after injection of (186)ReO(4) in two groups of animals treated with activity levels below the determined maximum tolerable activity as compared to controls.


CONCLUSIONS
These results indicate that the use of (186)ReO(4)(-) in the treatment of NIS-expressing neuroendocrine tumours is feasible and support the concept of using NIS as a therapeutic target for (186)ReO(4)(-).
Riese
Christoph G U
CG
Department of Nuclear Medicine, University of Marburg, Marburg, Germany. Riesec@students.uni-marburg.de
Seitz
Stephan
S
Schipper
Meike L
ML
Behr
Thomas M
TM
D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D011868:Radioisotopes; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use*; D027981:Symporters / Q000235:genetics*; D014018:Tissue Distribution; D014162:Transfection; D000099209:Sodium-Iodide Symporters
D011868:Radioisotopes; D012211:Rhenium; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C015428:perrhenate