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Updated: Sep 20, 2026
Intracranial Injection of Adeno-associated Viral Vectors
Published on: November 17, 2010
Molecular imaging of gene expression and efficacy following adenoviral-mediated brain tumor gene therapy
Alnawaz Rehemtulla1, Daniel E Hall, Lauren D Stegman
1University of Michigan School of Medicine, USA.
Abstract:
Cancer gene therapy is an active area of research relying upon the transfer and subsequent expression of a therapeutic transgene into tumor cells in order to provide for therapeutic selectivity. Noninvasive assessment of therapeutic response and correlation of the location, magnitude, and duration of transgene expression in vivo would be particularly useful in the development of cancer gene therapy protocols by facilitating optimization of gene transfer protocols, vector development, and prodrug dosing schedules. In this study, we developed an adenoviral vector containing both the therapeutic transgene yeast cytosine deaminase (yCD) along with an optical reporter gene (luciferase). Following intratumoral injection of the vector into orthotopic 9 L gliomas, anatomical and diffusion-weighted MR images were obtained over time in order to provide for quantitative assessment of overall therapeutic efficacy and spatial heterogeneity of cell kill, respectively. In addition, bioluminescence images were acquired to assess the duration and magnitude of gene expression. MR images revealed significant reduction in tumor growth rates associated with yCD/5-fluorocytosine (5FC) gene therapy. Significant increases in mean tumor diffusion values were also observed during treatment with 5FC. Moreover, spatial heterogeneity in tumor diffusion changes were also observed revealing that diffusion magnetic resonance imaging could detect regional therapeutic effects due to the nonuniform delivery and/or expression of the therapeutic yCD transgene within the tumor mass. In addition, in vivo bioluminescence imaging detected luciferase gene expression, which was found to decrease over time during administration of the prodrug providing a noninvasive surrogate marker for monitoring gene expression. These results demonstrate the efficacy of the yCD/5FC strategy for the treatment of brain tumors and reveal the feasibility of using multimodality molecular and functional imaging for assessment of gene expression and therapeutic efficacy.
Insights
This study developed a dual-gene adenoviral vector for cancer gene therapy, enabling noninvasive monitoring of therapeutic response and gene expression in brain tumors using advanced imaging techniques.
Area of Science:
- Oncology
- Molecular Biology
- Medical Imaging
Background:
- Cancer gene therapy aims for selective tumor cell targeting via transgene expression.
- Noninvasive monitoring of transgene expression and therapeutic effects is crucial for optimizing gene therapy protocols.
Purpose of the Study:
- To develop and evaluate an adenoviral vector encoding both a therapeutic gene (yeast cytosine deaminase, yCD) and a reporter gene (luciferase).
- To assess the efficacy of the yCD/5-fluorocytosine (5FC) gene therapy strategy in orthotopic gliomas using multimodality imaging.
Main Methods:
- Development of a dual-function adenoviral vector carrying yCD and luciferase genes.
- Intratumoral injection of the vector into 9 L gliomas in vivo.
- Longitudinal assessment using anatomical MRI, diffusion-weighted MRI, and bioluminescence imaging.
Main Results:
- MR imaging showed reduced tumor growth rates and increased tumor diffusion values with yCD/5FC treatment.
- Diffusion MRI detected spatial heterogeneity in therapeutic effects, indicating nonuniform transgene delivery/expression.
- Bioluminescence imaging confirmed luciferase expression, decreasing over time, serving as a noninvasive marker for gene expression.
Conclusions:
- The yCD/5FC gene therapy strategy is effective for treating brain tumors.
- Multimodality imaging combining molecular and functional techniques is feasible for assessing gene expression and therapeutic efficacy in cancer gene therapy.
