In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas.
Radioactive iodide uptake (RAIU) in thyroid follicular epithelial cells, mediated by the sodium iodide symporter (NIS), is the first rate-limiting step in iodide accumulation which provides a mechanism for effective radioiodide treatment for patients with thyroid cancer. We hypothesize that NIS gene transfer to non-thyroid tumor cells will enhance intracellular radioiodide accumulation and result in better tumor control. Here, we performed non-invasive tumor imaging and (131)I therapy studies using rats bearing intracerebral F98 gliomas that have been retrovirally transduced with human NIS. Our results show that: (1) NIS is expressed in the intracerebral F98/NIS gliomas; (2) F98/NIS gliomas can be imaged by (99m)TcO(4) (whose uptake is also mediated by NIS) and (123)I scintigraphy; (3) significant amounts of radioiodide were retained in the tumors at 24 h after (123)I injection; (4) RAIU and NIS expression in the thyroid gland can be reduced by feeding a thyroxine-supplemented diet; and (5) survival time was increased in rats bearing F98/hNIS tumors by (131)I treatment. These studies warrant further investigating tumor imaging and therapeutic strategies based on NIS gene transfer followed by radioiodide administration in a variety of human cancers.
Cho
J-Y
JY
Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH 43210-1218, USA.
Shen
D H Y
DH
Yang
W
W
Williams
B
B
Buckwalter
T L F
TL
La Perle
K M D
KM
Hinkle
G
G
Pozderac
R
R
Kloos
R
R
Nagaraja
H N
HN
Barth
R F
RF
Jhiang
S M
SM
D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D005910:Glioma / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D023421:Models, Animal; D051381:Rats; D011916:Rats, Inbred F344; D012190:Retroviridae / Q000235:genetics; D027981:Symporters / Q000032:analysis / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism; D013974:Thyroxine / Q000627:therapeutic use; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D027981:Symporters; D013974:Thyroxine; D000099209:Sodium-Iodide Symporters