Effects of dose, intervention time, and radionuclide on sodium iodide symporter (NIS)-targeted radionuclide therapy.
The sodium iodide symporter (NIS) mediates iodide uptake into thyrocytes and is the molecular basis of thyroid radioiodine therapy. We previously have shown that NIS gene transfer into the F98 rat gliomas facilitated tumor imaging and increased survival by radioiodine. In this study, we show that: (1) the therapeutic effectiveness of (131)I in prolonging the survival time of rats bearing F98/hNIS gliomas is dose- and treatment-time-dependent; (2) the number of remaining NIS-expressing tumor cells decreased greatly in RG2/hNIS gliomas post (131)I treatment and was inversely related to survival time; (3) 8 mCi each of (125)I/(131)I is as effective as 16 mCi (131)I alone, despite a smaller tumor absorbed dose; (4) (188)ReO(4), a potent beta(-) emitter, is more efficient than (131)I to enhance the survival of rats bearing F98/hNIS gliomas. These studies demonstrate the importance of radiopharmaceutical selection, dose, and timing of treatment to optimize the therapeutic effectiveness of NIS-targeted radionuclide therapy following gene transfer into gliomas.
Shen
D H Y
DH
Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210-1218, USA.
Marsee
D K
DK
Schaap
J
J
Yang
W
W
Cho
J-Y
JY
Hinkle
G
G
Nagaraja
H N
HN
Kloos
R T
RT
Barth
R F
RF
Jhiang
S M
SM
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D015316:Genetic Therapy; D005910:Glioma / Q000378:metabolism / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium; D027981:Symporters; D000099209:Sodium-Iodide Symporters