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Monitoring early tumor response to drug therapy with diffuse optical tomography

J. Biomed. Opt. 17, 016014 (Feb 08, 2012); http://dx.doi.org/10.1117/1.JBO.17.1.016014

Molly L. Flexman, Fotios Vlachos, Hyun Keol Kim, and Andreas H. Hielscher

Columbia University, New York, Department of Biomedical Engineering, New York, New York 10027

Shashank R. Sirsi and Mark A. Borden

Columbia University, New York, Department of Chemical Engineering, New York, New York 10027

University of Colorado, Boulder, Department of Mechanical Engineering, Boulder, Colorado 80309

Jianzhong Huang, Tessa B. Johung, Jeffrey W. Gander, Ari R. Reichstein, Darrell J. Yamashiro, and Jessica J. Kandel

Columbia University, New York, Department of Surgery, New York, New York 10032

Sonia L. Hernandez

Columbia University, New York, Department of Pediatrics and Pathology, New York, New York 10032

Brooke S. Lampl

Columbia University, New York, Department of Radiology, New York, New York 10032

Antai Wang

Columbia University, New York, Department of Biostatistics, Mailman School of Public Health, New York, New York 10032

Columbia University, New York, Department of Electrical Engineering, New York, New York 10027

Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy—thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

© 2012 Society of Photo-Optical Instrumentation Engineers

History
Received Sep 23, 2011
Accepted Nov 30, 2011
Revised Nov 25, 2011
Published online Feb 08, 2012
Citation
Molly L. Flexman, Fotios Vlachos, Hyun Keol Kim, Shashank R. Sirsi, Jianzhong Huang, Sonia L. Hernandez, Tessa B. Johung, Jeffrey W. Gander, Ari R. Reichstein, Brooke S. Lampl, Antai Wang, Mark A. Borden, Darrell J. Yamashiro, Jessica J. Kandel and Andreas H. Hielscher, "Monitoring early tumor response to drug therapy with diffuse optical tomography", J. Biomed. Opt. 17, 016014 (Feb 08, 2012); http://dx.doi.org/10.1117/1.JBO.17.1.016014

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