In vivo magnetic resonance imaging and spectroscopy identifies oncolytic adenovirus responders

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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. What's new? Using oncolytic viruses and other immunological therapies against tumors could be a lot more successful if clinicians had a way to identify which patients would benefit from such treatments. Could magnetic resonance imaging (MRI) and spectroscopy (MRS) provide assistance? In this paper, the authors tested the ability of MRI and MRS to show how tumors responded to oncolytic viruses. Both in a hamster model and in a human patient, the imaging and spectroscopy data provided good indications of how the treatment was proceeding, suggesting these tools might be more broadly useful for monitoring the early stages of treatment with oncolytic viruses. © 2013 UICC.

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Hemminki, O., Immonen, R., Närväinen, J., Kipar, A., Paasonen, J., Jokivarsi, K. T., … Hemminki, A. (2014). In vivo magnetic resonance imaging and spectroscopy identifies oncolytic adenovirus responders. International Journal of Cancer, 134(12), 2878–2890. https://doi.org/10.1002/ijc.28615

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