Evaluation of Adenoviral Oncolytic Effect on Glioma Spheroids by 18F-DG Positron-Emission Tomography

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Abstract:

Multicellular tumor spheroids are used as a model to assess the efficacy of replicating oncolytic adenoviruses. As most assays used to assess cellular viability are unsuitable for oncolytic viruses because of ongoing viral replication, we have used positron emission tomography (PET) to sequentially determine the incorporation of 18F-labeled deoxyglucose (18F-DG) as a measure of viability and compared the results to more commonly used assays for measuring the effect of oncolytic therapy. Glioma monolayer cultures and spheroids were infected with wild-type replicating adenovirus and viability was measured by 18F-DG incorporation, WST-1 assay, crystal violet assay, and spheroid volume 2 to 10 days following infection. Results show that volume measurements in adenovirus-infected spheroids are confounded by the cytopathic effect occurring in infected cells. 18F-DG PET provides a useful method to assess small differences in cell number and viability following oncolytic viral therapy in glioma monolayer cultures and spheroids without the need for disintegration of these cultures. Moreover, using 18F-DG PET, repeated sequential measurements of spheroid viability can be made, decreasing the required number of spheroids per experiment. This is a valuable feature when using spheroids derived from limited amounts of patient material.

Keywords: Fluoro-deoxyglucose; Glioma; Multicellular spheroid; Oncolytic virus; Positron emission tomography

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096504007783338304

Affiliations: 1: Department of Neurosurgery, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands 2: Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands 3: Department of Medical Oncology, Division of Gene Therapy, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands 4: Department of Neurosurgery, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands, Department of Medical Oncology, Division of Gene Therapy, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands

Publication date: October 1, 2007

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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