MTCT: PET monitors gene therapy in glioma

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PET strategies are very useful in monitoring the distribution and kinetics of vector-mediated gene expression, as well as the response to therapy in malignant glioma, according to a presentation last week at the Molecular Targets and Cancer Therapeutics (MTCT) conference in Boston.

Alexandra Winkeler, PhD, and colleagues performed the study at Max Planck-Institute for Neurological Research, Center for Molecular Medicine Cologne and department of neurology at the University of Cologne and Klinikum Fulda, Germany.

“We use molecular imaging techniques to non-invasively assess certain biological processes, like gene expression, signal transduction, protein-protein interaction and transcriptional regulation,” said Winkeler. “We can localize this biological process in a three dimensional manner, quantify and follow the dynamics of the process over time in the same experimental subject.”

In the study, the herpes simplex virus type 1 thymidine kinase gene (HSV-1-tk) was used as a marker gene for the direct noninvasive in vivo localization of thymidine kinase (TK) expression by PET. When F18-labeled tracer is injected into an animal or patient, it crosses from the plasma membrane into the cell and the cells that express the exogenous gene will phosphorylate the tracer resulting in the tracer’s accumulation inside the cell, explained Winkeler.

FDG-PET helps in characterizing the tumor tissue before the gene therapy.

“It is important to identify the viable part of the tumor tissue by FDG-PET before we introduce our viral vector,” said Winkeler.

The researchers addressed the question: “Does the primary transduction efficiency that we measure by FDG-PET correlate with the therapeutic effect measured by change of tumor volume or the change in fluoro-3'-deoxy- L-thymidine (FLT) uptake?”

The pre-clinical results showed transduction efficiency measured by FDG-PET correlated with the response to gene therapy monitored by change in FLT. However, in the clinical studies, there was a slight decrease in FLT accumulation in the early phase of the therapy, but there was no long-term decrease in FLT upon follow-up.

“The problem was very limited distribution of the vector within the targeted tissue,” Winkeler noted. To overcome this problem the investigators are trying to invent new type of vector-hybrid-vector system and the study is ongoing.

“PET is very important in gene therapy--in characterizing the tumor, identifying where to apply the gene therapeutic vector, quantifying vector mediated gene expression and following response to therapy,” summarized Winkeler.