Molecular imaging for stem cell therapy in the brain

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Abstract

Molecular imaging is one of the methods to follow-up stem cell therapy by visualization in the brain. In a recent article in Stem Cell Research & Therapy, Micci et al. offer a thorough discussion of the advantages and disadvantages of this method and their roles in the future. The authors are among the very first who have implemented recently introduced molecular imaging techniques in experimental research and clinical practice.

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Molecular imaging of brain tumors personal experience and review of the literature.

George B. Schaller, Nora Sandu, F Cornelius … (2008)

Non-invasive energy metabolism measurements in brain tumors in vivo are now performed widely as molecular imaging by positron emission tomography. This capability has developed from a large number of basic and clinical science investigations that have cross fertilized one another. Apart from precise anatomical localization and quantification, the most intriguing advantage of such imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, molecular imaging represents a key-technology in translational research, helping to develop experimental protocols that may later be applied to human patients. Common clinical indications for molecular imaging of primary brain tumors therefore contain (i) primary brain tumor diagnosis, (ii) identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), and (iii) prediction of treatment response by measurement of tumor perfusion, or ischemia. The key-question remains whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival. Molecular imaging may identify early disease and differentiate benign from malignant lesions. Moreover, an early identification of treatment effectiveness could influence patient management by providing objective criteria for evaluation of therapeutic strategies for primary brain tumors. Specially, its novel potential to visualize metabolism and signal transduction to gene expression is used in reporter gene assays to trace the location and temporal level of expression of therapeutic and endogenous genes. The authors present here illustrative data of PET imaging: the thymidine kinase gene expression in experimentally transplanted F98 gliomas in cat brain indicates, that [(18)F]FHBG visualizes cells expressing TK-GFP gene in transduced gliomas as well as quantities and localizes transduced HSV-1-TK expression if the blood brain barrier is disrupted. The higher uptake of [(18)F]FLT in the wild-type compared to the transduced type may demonstrate the different doubling time of both tumor tissues suggesting different cytosolic thymidine kinase activity. Molecular imaging probes are developed to image the function of targets without disturbing them or as drug in oder to modify the target's function. This is transfer of gene therapy's experimental knowledge into clinical applications. Molecular imaging closes the gap between in vitro to in vivo integrative biology of disease.

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Strategies for molecular imaging dementia and neurodegenerative diseases

Bernhard Schaller (2008)

Dementia represents a heterogeneous term that has evolved to describe the behavioral syndromes associated with a variety of clinical and neuropathological changes during continuing degenerative disease of the brain. As such, there lacks a clear consensus regarding the neuropsychological and other constituent characteristics associated with various cerebrovascular changes in this disease process. But increasing this knowledge has given more insights into memory deterioration in patients suffering from Alzheimer’s disease and other subtypes of dementia. The author reviews current knowledge of the physiological coupling between cerebral blood flow and metabolism in the light of state-of-the-art-imaging methods and its changes in dementia with special reference to Alzheimer’s disease. Different imaging techniques are discussed with respect to their visualizing effect of biochemical, cellular, and/or structural changes in dementia. The pathophysiology of dementia in advanced age is becoming increasingly understood by revealing the underlying basis of neuropsychological changes with current imaging techniques, genetic and pathological features, which suggests that alterations of (neuro) vascular regulatory mechanisms may lead to brain dysfunction and disease. The current view is that cerebrovascular deregulation is seen as a contributor to cerebrovascular pathologies, such as stroke, but also to neurodegenerative conditions, such as Alzheimer’s disease. The better understanding of these (patho) physiological mechanisms may open an approach to new interventional strategies in dementia to enhance neurovascular repair and to protect neurovascular coupling.

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Molecular imaging of brain tumors: a bridge between clinical and molecular medicine?

B Schaller, M Modo, M Buchfelder (2015)

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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Contributors

Bernhard Schaller: bernhardjschaller@gmail.com

Journal

Journal ID (nlm-ta): Stem Cell Res Ther

Journal ID (iso-abbrev): Stem Cell Res Ther

Title: Stem Cell Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-6512

Publication date (Electronic): 18 December 2015

Publication date PMC-release: 18 December 2015

Publication date Collection: 2015

Volume: 6

Electronic Location Identifier: 252

Affiliations

[ ]University of Oxford, Wellington Square, Oxford, OX1 2JD UK

[ ]University of Southampton, University Road, Southampton, SO17 1BJ UK

[ ]Department of Anesthesiology and Peri-operative Medicine, University of Manitoba, Winnipeg, MB R3T 2N2 Canada

Article

Publisher ID: 242

DOI: 10.1186/s13287-015-0242-7

PMC ID: 4683971

SO-VID: c5f98763-4f43-4ce7-815a-7e0cff61e51a

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Molecular imaging for stem cell therapy in the brain

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Most cited references 15

Molecular imaging of brain tumors personal experience and review of the literature.

Strategies for molecular imaging dementia and neurodegenerative diseases

Molecular imaging of brain tumors: a bridge between clinical and molecular medicine?

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