Molecular Imaging of Brain Tumors: A Bridge Between Clinical and Molecular Medicine?

Abstract

As the research on cellular changes has shed invaluable light on the pathophysiology and biochemistry of brain tumors, clinical and experimental use of molecular imaging methods is expanding and allows quantitative assessment. The term molecular imaging is defined as the in vivo characterization and measurement of biologic processes at the cellular and molecular level. Molecular imaging sets forth to probe the molecular abnormalities that are the basis of disease rather than to visualize the end effects of these molecular alterations and, therefore, provides different additional biochemical or molecular information about primary brain tumors compared to histological methods "classical" neuroradiological diagnostic studies. Common clinical indications for molecular imaging contain primary brain tumor diagnosis and identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), prediction of treatment response by measurement of tumor perfusion, or ischemia. The interesting key question remains not only whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival, but also whether it identifies early disease and differentiates benign from malignant lesions. Moreover, an early identification of treatment success or failure by molecular imaging could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies. Specially, as molecular imaging represents a novel technology for visualizing metabolism and signal transduction to gene expression, reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. Molecular imaging probes and drugs are being developed to image the function of targets without disturbing them and in mass amounts to modify the target's function as a drug. Molecular imaging helps to close the gap between in vitro and in vivo integrative biology of disease.

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“…Cytolytic viruses and genes coding for antitumor cytokines, prodrug-converting enzymes and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors (1). Novel brain tumor treatment strategies that involve transplantation or infusion of cells that seek out invading tumor cells demand thorough in vivo monitoring (3)(4)(5)(6)(7)(8)15,16). In particular, NSCs have attracted great interest because they have demonstrated tropism to tumor cells and even long-distance migration to single tumor cells (17,18).…”

“…This advancement has led to significantly increased understanding of the spatiotemporal kinetics of NSC engraftment, localization, viability and proliferation in living subjects (29)(30)(31). A major advance in molecular imaging has been the extension of noninvasive reporter gene assays from molecular and cellular biology into in vivo multimodality imaging platforms (15,29,30). The ability to control the activity of transplanted cells presupposes that it is possible to visualize the presence, location and activity of stem cells in vivo.…”

Molecular Medicine Successes in Neuroscience

“…Molecular imaging is generally defined as the in vivo characterization and measurement of biological processes at the cellular and molecular level (2). In contrast to visualizing the terminal effects of disease, molecular imaging probes the molecular alterations underlying disease, providing additional biochemical or molecular information compared with histological methods and classic neuroradiological diagnostic studies (3).…”

“…In particular, molecular imaging represents a fresh technology for visualizing metabolism and signal transduction to gene expression. Reporter gene assays, used to trace the location and temporal level of therapeutic and endogenous gene expression, such as in brain tumors (2), open a window to future treatment modalities. Molecular imaging drugs and probes, such as positron-emission tomography (PET), are being developed to image the function of targets without disturbing them, and are developed in mass amounts to modify the target's function as a pharmacological substance (4).…”

Stem Cell Transplantation in Neuroscience: The Role of Molecular Imaging

“…Further strategies relying on reporter genes might in the near future provide interesting new possibilities to current strategies and broaden some of the current limitations [7,9]. Current problems of molecular imaging in neurosciences are a low contrast and crossing of the BBB [2].…”