Neuroimaging clinics of North America
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Neuroimaging Clin. N. Am. · Nov 2002
ReviewInnovations in design and delivery of chemotherapy for brain tumors.
Effectiveness of chemotherapy in patients with brain tumors is hampered by the presence of the blood-brain barrier and drug resistance. In recent years, significant progress has been made in devising innovative methods of design and delivery of chemotherapy for brain tumors. This article has surveyed the issues of blood-brain barrier and drug resistance and explored some of the strategies used to circumvent problems associated with chemotherapy failure in patients with brain tumors.
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A wide variety of metabolic features of brain tumors can be imaged using PET, including glucose metabolism, blood flow, oxygen consumption, amino acid metabolism, and lipid synthesis. Currently, FDG is the most widely available PET tracer for body imaging and brain imaging. Malignant brain tumors, like many other soft tissue tumors, show increased glucose metabolism, which is reflected on FDG-PET imaging. ⋯ Other tracers, such as 11C-methionine and FCH, also avidly accumulate in brain tumors and have the advantage of low background cortical activity. The relationship between degree of uptake of these agents and tumor grade is not established. These tracers may be useful in specific clinical situations, however, such as tumor localization for treatment planning or evaluation of low-grade tumors.
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The grave outlook for malignant glioma patients in spite of improvements to current modalities has ushered in new approaches to therapy. Viruses have emerged on the scene and gained attention for their ability to play essentially two roles: first, as vectors for therapeutic gene delivery and second, as engineered infectious agents capable of selectively lysing tumor cells. ⋯ Clinical oncolytic studies, on the other hand, have evaluated a conditionally replicating HSV as an antineoplastic agent. Despite some promise afforded by these trials, further studies are warranted; the investigation of additional viruses to play these roles is inevitable and is now precedented.
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Neuroimaging Clin. N. Am. · Nov 2002
ReviewViral imaging in gene therapy noninvasive demonstration of gene delivery and expression.
Gene therapy is a rapidly developing modality of treatment, with applications in acquired and inherited disorders. Gene delivery vehicles ("vectors") are the main impediment in the evolution of gene therapy into a clinically acceptable mainstream therapy. Vectors based on viral particles are the most commonly used vehicles to carry genes to the organs and tissues of interest. ⋯ Recent progress in viral vector production and better understanding of molecular aspects of vector delivery and targeting issues has created the need for imaging techniques that would be useful in addressing the problems and opportunities inherent in viral gene therapy development. Two integral components of gene therapy monitoring, the imaging of gene delivery and the imaging of resultant exogenous gene expression, are recognized. These molecular imaging components provide a realistic means for assessment of safety and efficacy of preclinical and clinical development of gene therapy.
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As an immunization platform for brain tumors, dendritic cells supply an impressive host of advantages. On the simplest level, they provide the safety and tumor-specificity so wanted by current therapeutic options. ⋯ Directions to take now include the identification of new tumor-specific and tumor-associated antigens; the determination of the optimal dendritic cell subtype, generation, loading method, maturation state, dose, and route of delivery for immunizations; the further characterization of dendritic cells and their activities; and, potentially, the discovery of ways to pulse dendritic cells efficiently in vivo. Preclinical studies continue to play an important role in refining this form of active immunotherapy.