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      Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) in Preclinical Studies of Antivascular Treatments

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          Abstract

          Antivascular treatments can either be antiangiogenic or targeting established tumour vasculature. These treatments affect the tumour microvasculature and microenvironment but may not change clinical measures like tumour volume and growth. In research on antivascular treatments, information on the tumour vasculature is therefore essential. Preclinical research is often used for optimization of antivascular drugs alone or in combined treatments. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an in vivo imaging method providing vascular information, which has become an important tool in both preclinical and clinical research. This review discusses common DCE-MRI imaging protocols and analysis methods and provides an overview of preclinical research on antivascular treatments utilizing DCE-MRI.

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          Tumor response to radiotherapy regulated by endothelial cell apoptosis.

          About 50% of cancer patients receive radiation therapy. Here we investigated the hypothesis that tumor response to radiation is determined not only by tumor cell phenotype but also by microvascular sensitivity. MCA/129 fibrosarcomas and B16F1 melanomas grown in apoptosis-resistant acid sphingomyelinase (asmase)-deficient or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200 to 400% faster than tumors on wild-type microvasculature. Thus, endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Moreover, these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, they were resistant to single-dose radiation up to 20 grays (Gy). These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range.
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            Clinical translation of angiogenesis inhibitors.

            Angiogenesis inhibitors are a new class of drugs, for which the general rules involving conventional chemotherapy might not apply. The successful translation of angiogenesis inhibitors to clinical application depends partly on the transfer of expertise from scientists who are familiar with the biology of angiogenesis to clinicians. What are the most common questions that clinicians ask as they begin to test angiogenesis inhibitors in cancer clinical trials?
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              High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis.

              The authors review the theoretical basis of determination of cerebral blood flow (CBF) using dynamic measurements of nondiffusible contrast agents, and demonstrate how parametric and nonparametric deconvolution techniques can be modified for the special requirements of CBF determination using dynamic MRI. Using Monte Carlo modeling, the use of simple, analytical residue models is shown to introduce large errors in flow estimates when actual, underlying vascular characteristics are not sufficiently described by the chosen function. The determination of the shape of the residue function on a regional basis is shown to be possible only at high signal-to-noise ratio. Comparison of several nonparametric deconvolution techniques showed that a nonparametric deconvolution technique (singular value decomposition) allows estimation of flow relatively independent of underlying vascular structure and volume even at low signal-to-noise ratio associated with pixel-by-pixel deconvolution.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                07 November 2012
                December 2012
                : 4
                : 4
                : 563-589
                Affiliations
                Department of Experimental Clinical Oncology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; Email: wittenborn@ 123456oncology.dk (T.W.); mike@ 123456oncology.dk (M.R.H.)
                Author notes
                [* ] Author to whom correspondence should be addressed; Email: thomas@ 123456oncology.dk ; Tel.: +45-78463589; Fax: +45-86197109
                Article
                pharmaceutics-04-00563
                10.3390/pharmaceutics4040563
                3834929
                24300371
                67b707ef-6fa9-4e7f-8f52-578d6383521d
                © 2012 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 29 June 2012
                : 29 October 2012
                : 30 October 2012
                Categories
                Review

                dce-mri,angiogenesis inhibitors,vascular disrupting agents,preclinical studies

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