Characterization of Experimental Gliomas by Multi-Modal Molecular Imaging

Background: Molecular imaging allows the non-invasive longitudinal characterization of disease specific alterations in vivo not only in experimental models but also in humans. This technology is increasingly used for assessing cancer-associated molecular markers as the basis for implementation of disease-stage specific therapies.

Aim: The goal of this study was to assess the growth dynamics of human gliomas in a mouse model by multi-modal imaging.

Methods: Imaging of subcutaneous and intracranial growing and stably luciferase (LUC) expressing human U87 and Gli36 gliomas in nude mice (n=27) was performed employing bioluminescence imaging (BLI), fluorescence resonance imaging (FRI), positron emission tomography (PET) and computed tomography (CT). Molecular targets for imaging comprised assessment of expression levels of LUC (luciferin; n=16), matrix metalloproteinase (MMP; MMPsense680, n=11), glucose consumption (F18-fluorodeoxyglucose (FDG); n=11), amino acid transport (C11-methionine; n=3), and proliferation (F18-fluorothymidine (FLT); n=4). Some animals were followed after treatment with temozolomide (n=7).

Results: Repetitive BLI of luciferase expressing gliomas revealed a correlation of signal intensity (photons/s) with tumor growth as determined by caliper measurements (mm³) with maximum values in larger tumors up to 5×10⁹ photons/s. Active MMPs were detectable in all animals with maximum values up to 4×10¹⁰ photons/s/cm²/steradian/microwatt/cm². Comparison of optical imaging with PET parameters demonstrated that optical imaging is less capable of reflecting inhomogeneities within a tumor with regards to differentiation of viable tissue from central necrosis of larger tumors. Temozolomide treatment lead to a decrease in the LUC signal, and, interestingly, to a relative increase of MMP activity.

Conclusion: Optical imaging is a valuable, relatively inexpensive and rapid technology to non-invasively analyze growth dynamics of experimental gliomas. It should be pointed out that tomographic optical methods including scatter and attenuation correction still have to be developed. PET adds important tomographic molecular information which can be translated directly into human application.