title: Tumor-specific targeting with modified Sindbis viral vectors: evaluation with optical imaging and positron emission tomography in vivo.
abstract: OBJECTIVE
  Sindbis virus (SINV) infect tumor cells specifically and systemically throughout the body. Sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. The ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option.
  
  
  METHODS
  The tumor specificity of SINV is mediated by the 67-kDa laminin receptor (LR). We probed different cancer cell lines for their LR expression and, to determine the specific role of LR-expression in the infection cycle, used different molecular imaging strategies, such as bioluminescence, fluorescence molecular tomography, and positron emission tomography, to evaluate SINV-mediated infection in vitro and in vivo.
  
  
  RESULTS
  All cancer cell lines showed a marked expression of LR. The infection rates of the SINV particles, however, differed significantly among the cell lines.
  
  
  CONCLUSIONS
  We used novel molecular imaging techniques to visualize vector delivery to different neoplatic cells. SINV infection rates proofed to be not solely dependent on cellular LR expression. Further studies need to evaluate the herein discussed ways of cellular infection and viral replication.
authors: Nuclear Medicine Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, USA. lars.stelter@charite.de
authors: Lars
authors: L
authors: Stelter
authors: Jen-Chieh
authors: JC
authors: Tseng
authors: Armen
authors: A
authors: Torosjan
authors: Brandi
authors: B
authors: Levin
authors: Valerie A
authors: VA
authors: Longo
authors: Nagavarakishore
authors: N
authors: Pillarsetty
authors: Pat
authors: P
authors: Zanzonico
authors: Daniel
authors: D
authors: Meruelo
authors: Steven M
authors: SM
authors: Larson
mesh_terms: D000818:Animals; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005456:Fluorescent Dyes; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D057054:Molecular Imaging / Q000379:methods*; D061848:Optical Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism; D012845:Sindbis Virus / Q000235:genetics*; D014162:Transfection
chemical_list: D005456:Fluorescent Dyes; D017474:Receptors, Laminin