title: A steep radioiodine dose response scalable to humans in sodium-iodide symporter (NIS)-mediated radiovirotherapy for prostate cancer.
abstract: The sodium-iodide symporter (NIS) directs the uptake and concentration of iodide in thyroid cells. We have extended the use of NIS-mediated radioiodine therapy to prostate cancer. We have developed a prostate tumor specific conditionally replicating adenovirus that expresses hNIS (Ad5PB_RSV-NIS). For radiovirotherapy to be effective in humans, the radioiodine dose administered in the pre-clinical animal model should scale to the range of acceptable doses in humans. We performed (131)I dose-response experiments aiming to determine the dose required in mice to achieve efficient radiovirotherapy. Efficacy was determined by measuring tumor growth and survival times. We observed that individual tumors display disparate growth rates that preclude averaging within a treatment modality indicating heterogeneity of growth rate. We further show that a statistic and stochastic approach must be used when comparing the effect of an anti-cancer therapy on a cohort of tumors. Radiovirotherapy improves therapeutic value over virotherapy alone by slowing the rate of tumor growth in a more substantial manner leading to an increase in survival time. We also show that the radioiodine doses needed to achieve this increase scaled well within the current doses used for treatment of thyroid cancer in humans.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetes, Metabolism, Nutrition, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Trujillo
authors.forename: M J
authors.initials: MJ
authors.lastname: Oneal
authors.forename: S
authors.initials: S
authors.lastname: McDonough
authors.forename: R
authors.initials: R
authors.lastname: Qin
authors.forename: J C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D048708:Cell Growth Processes / Q000528:radiation effects; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy* / Q000821:virology; D015996:Survival Rate; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters