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Blood-Tumor Barrier Normalization Effects on Cytotoxic Drug Delivery to Brain Tumors

[+] Author Affiliations
Gregory L. Pishko, Morad Nasseri, Seymur Gahramanov, Leslie L. Muldoon

Oregon Health & Science University, Portland, OR

Edward A. Neuwelt

Oregon Health & Science University, Portland, ORVeterans Affairs Medical Center, Portland, OR

Paper No. SBC2013-14648, pp. V01AT21A005; 2 pages
doi:10.1115/SBC2013-14648
From:
  • ASME 2013 Summer Bioengineering Conference
  • Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tissue Engineering; Cerebral Aneurysms; Computational Biofluid Dynamics; Device Design, Human Dynamics, and Rehabilitation; Drug Delivery and Disease Treatment; Engineered Cellular Environments
  • Sunriver, Oregon, USA, June 26–29, 2013
  • Conference Sponsors: Bioengineering Division
  • ISBN: 978-0-7918-5560-7
  • Copyright © 2013 by ASME

abstract

The blood-brain barrier (BBB) restricts delivery of anti-cancer drugs to brain tumors, but the leaky neovasculature of the blood-tumor barrier (BTB) permits systemically delivered cytotoxic agents to reach the tumor. Anti-angiogenic therapies such as bevacizumab (BEV) have been shown to “normalize” brain tumor vasculature,1 but the impact on chemotherapy delivery remains unclear.2 The goal of this study was to use magnetic resonance imaging (MRI) to investigate the consequences of BTB normalization, via BEV, on temozolomide (TMZ) chemotherapy. Non-invasive MRI techniques were used to track the transport of a chemotherapy surrogate, a low molecular contrast agent (Gd-DTPA), in an intracerebrally implanted human glioma. MRI-derived Gd-DTPA concentration curves were fit to a transvascular exchange model to measure vascular permeability changes and were used to quantify initial area under the gadolinium curve (IAUGC) over the course of treatment.

Copyright © 2013 by ASME

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