title: SPECT/CT imaging of hNIS-expression after intravenous delivery of an oncolytic adenovirus and 131I.
abstract: Oncolytic adenoviruses can be engineered for better tumor selectivity, gene delivery and be armed for imaging and concentrating radionuclides into tumors for synergistic oncolysis. We constructed Ad5/3-hTERT-hNIS where replication is controlled by hTERT-promoter. Ad5/3-hTERT-hNIS expresses hNIS for imaging of transgene expression and for treatment of infected tumors by radioiodine. Ad5/3-hTERT-hNIS efficiently killed prostate cancer cells and induced iodine uptake in vitro and in vivo after intratumoral virus administration. Survival of mice treated with intravenous Ad5/3-hTERT-hNIS significantly prolonged survival over mock or radioiodine only but the combination of virus with radioiodine was not more effective than virus alone. Temporal and spatial changes in hNIS-expression during therapy were detected with SPECT, demonstrating feasibility of evaluation of the combination therapy with hNIS-expressing adenoviruses and radioiodide.
authors.affiliation: Cancer Gene Therapy Group, Molecular Cancer Biology Program, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Rajecki
authors.forename: Mirkka
authors.initials: M
authors.lastname: Sarparanta
authors.forename: Tanja
authors.initials: T
authors.lastname: Hakkarainen
authors.forename: Mikko
authors.initials: M
authors.lastname: Tenhunen
authors.forename: Iulia
authors.initials: I
authors.lastname: Diaconu
authors.forename: Venla
authors.initials: V
authors.lastname: Kuhmonen
authors.forename: Kalevi
authors.initials: K
authors.lastname: Kairemo
authors.forename: Anna
authors.initials: A
authors.lastname: Kanerva
authors.forename: Anu J
authors.initials: AJ
authors.lastname: Airaksinen
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging; D064847:Multimodal Imaging; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters