title: Imaging of intratumoral inflammation during oncolytic virotherapy of tumors by 19F-magnetic resonance imaging (MRI).
abstract: BACKGROUND
  Oncolytic virotherapy of tumors is an up-coming, promising therapeutic modality of cancer therapy. Unfortunately, non-invasive techniques to evaluate the inflammatory host response to treatment are rare. Here, we evaluate (19)F magnetic resonance imaging (MRI) which enables the non-invasive visualization of inflammatory processes in pathological conditions by the use of perfluorocarbon nanoemulsions (PFC) for monitoring of oncolytic virotherapy.
  
  
  RESULTS
  The Vaccinia virus strain GLV-1h68 was used as an oncolytic agent for the treatment of different tumor models. Systemic application of PFC emulsions followed by (1)H/(19)F MRI of mock-infected and GLV-1h68-infected tumor-bearing mice revealed a significant accumulation of the (19)F signal in the tumor rim of virus-treated mice. Histological examination of tumors confirmed a similar spatial distribution of the (19)F signal hot spots and CD68(+)-macrophages. Thereby, the CD68(+)-macrophages encapsulate the GFP-positive viral infection foci. In multiple tumor models, we specifically visualized early inflammatory cell recruitment in Vaccinia virus colonized tumors. Furthermore, we documented that the (19)F signal correlated with the extent of viral spreading within tumors.
  
  
  CONCLUSIONS
  These results suggest (19)F MRI as a non-invasive methodology to document the tumor-associated host immune response as well as the extent of intratumoral viral replication. Thus, (19)F MRI represents a new platform to non-invasively investigate the role of the host immune response for therapeutic outcome of oncolytic virotherapy and individual patient response.
authors: Department of Biochemistry, Biocenter, University of Wuerzburg, Wuerzburg, Germany.
authors: Stephanie
authors: S
authors: Weibel
authors: Thomas Christian
authors: TC
authors: Basse-Luesebrink
authors: Michael
authors: M
authors: Hess
authors: Elisabeth
authors: E
authors: Hofmann
authors: Carolin
authors: C
authors: Seubert
authors: Johanna
authors: J
authors: Langbein-Laugwitz
authors: Ivaylo
authors: I
authors: Gentschev
authors: Volker Jörg Friedrich
authors: VJ
authors: Sturm
authors: Yuxiang
authors: Y
authors: Ye
authors: Thomas
authors: T
authors: Kampf
authors: Peter Michael
authors: PM
authors: Jakob
authors: Aladar A
authors: AA
authors: Szalay
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005466:Fluorocarbons; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D009369:Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics; D062211:Spatio-Temporal Analysis; D014183:Transplantation, Heterologous; D014616:Vaccinia virus / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005466:Fluorocarbons; C067980:CD68 antigen, human; D000097382:CD68 Molecule