title: In vivo magnetic resonance imaging and spectroscopy identifies oncolytic adenovirus responders.
abstract: At present, it is not possible to reliably identify patients who will benefit from oncolytic virus treatments. Conventional modalities such as computed tomography (CT), which measure tumor size, are unreliable owing to inflammation-induced tumor swelling. We hypothesized that magnetic resonance imaging (MRI) and spectroscopy (MRS) might be useful in this regard. However, little previous data exist and neither oncolytic adenovirus nor immunocompetent models have been assessed by MRS. Here, we provide evidence that in T2-weighted MRI a hypointense core area, consistent with coagulative necrosis, develops in immunocompetent Syrian hamster carcinomas that respond to oncolytic adenovirus treatment. The same phenomenon was observed in a neuroblastoma patient while he responded to the treatment. With relapse at a later stage, however, the tumor of this patient became moderately hyperintense. We found that MRS of taurine, choline and unsaturated fatty acids can be useful early indicators of response and provide detailed information about tumor growth and degeneration. In hamsters, calprotectin-positive inflammatory cells (heterophils and macrophages) were found in abundance; particularly surrounding necrotic areas in carcinomas and T cells were significantly increased in sarcomas, when these had been treated with a granulocyte-macrophage colony-stimulating factor-producing virus, suggesting a possible link between oncolysis, necrosis (seen as a hypointense core in MRI) and/or immune response. Our study indicates that both MRI and MRS could be useful in the estimation of oncolytic adenovirus efficacy at early time points after treatment.
authors.affiliation: Cancer Gene Therapy Group Transplantation Laboratory & Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Hemminki
authors.forename: R
authors.initials: R
authors.lastname: Immonen
authors.forename: J
authors.initials: J
authors.lastname: Närväinen
authors.forename: A
authors.initials: A
authors.lastname: Kipar
authors.forename: J
authors.initials: J
authors.lastname: Paasonen
authors.forename: K T
authors.initials: KT
authors.lastname: Jokivarsi
authors.forename: H
authors.initials: H
authors.lastname: Yli-Ollila
authors.forename: P
authors.initials: P
authors.lastname: Soininen
authors.forename: K
authors.initials: K
authors.lastname: Partanen
authors.forename: T
authors.initials: T
authors.lastname: Joensuu
authors.forename: S
authors.initials: S
authors.lastname: Parvianen
authors.forename: S K
authors.initials: SK
authors.lastname: Pesonen
authors.forename: A
authors.initials: A
authors.lastname: Koski
authors.forename: M
authors.initials: M
authors.lastname: Vähä-Koskela
authors.forename: V
authors.initials: V
authors.lastname: Cerullo
authors.forename: S
authors.initials: S
authors.lastname: Pesonen
authors.forename: O H
authors.initials: OH
authors.lastname: Gröhn
authors.forename: A
authors.initials: A
authors.lastname: Hemminki
mesh_terms: D000256:Adenoviridae; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000473:pathology / Q000628:therapy; D002478:Cells, Cultured; D002794:Choline / Q000032:analysis; D006224:Cricetinae; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009336:Necrosis; D009447:Neuroblastoma / Q000473:pathology* / Q000628:therapy*; D050130:Oncolytic Virotherapy; D012509:Sarcoma / Q000473:pathology / Q000628:therapy; D013654:Taurine / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005231:Fatty Acids, Unsaturated; D013654:Taurine; D002794:Choline
keywords: MRI; MRS; adenovirus; cancer; oncolytic