title: In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas.
abstract: 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.
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH 43210-1218, USA.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Cho
authors.forename: D H Y
authors.initials: DH
authors.lastname: Shen
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: B
authors.initials: B
authors.lastname: Williams
authors.forename: T L F
authors.initials: TL
authors.lastname: Buckwalter
authors.forename: K M D
authors.initials: KM
authors.lastname: La Perle
authors.forename: G
authors.initials: G
authors.lastname: Hinkle
authors.forename: R
authors.initials: R
authors.lastname: Pozderac
authors.forename: R
authors.initials: R
authors.lastname: Kloos
authors.forename: H N
authors.initials: HN
authors.lastname: Nagaraja
authors.forename: R F
authors.initials: RF
authors.lastname: Barth
authors.forename: S M
authors.initials: SM
authors.lastname: Jhiang
mesh_terms: 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
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D013974:Thyroxine; D000099209:Sodium-Iodide Symporters