title: Monitoring early tumor response to drug therapy with diffuse optical tomography.
abstract: 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.
authors.affiliation: Columbia University, New York, Department of Biomedical Engineering, New York, New York 10027, USA.
authors.forename: Molly L
authors.initials: ML
authors.lastname: Flexman
authors.forename: Fotios
authors.initials: F
authors.lastname: Vlachos
authors.forename: Hyun Keol
authors.initials: HK
authors.lastname: Kim
authors.forename: Shashank R
authors.initials: SR
authors.lastname: Sirsi
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Huang
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Hernandez
authors.forename: Tessa B
authors.initials: TB
authors.lastname: Johung
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Gander
authors.forename: Ari R
authors.initials: AR
authors.lastname: Reichstein
authors.forename: Brooke S
authors.initials: BS
authors.lastname: Lampl
authors.forename: Antai
authors.initials: A
authors.lastname: Wang
authors.forename: Mark A
authors.initials: MA
authors.lastname: Borden
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Yamashiro
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Kandel
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Hielscher
mesh_terms: D000704:Analysis of Variance; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000068258:Bevacizumab; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005456:Fluorescent Dyes; D006454:Hemoglobins / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010108:Oxyhemoglobins / Q000378:metabolism; D055420:Perfusion Imaging; D037121:Plant Lectins; D041622:Tomography, Optical / Q000379:methods*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D005456:Fluorescent Dyes; D006454:Hemoglobins; D010108:Oxyhemoglobins; D037121:Plant Lectins; D000068258:Bevacizumab; C100003:deoxyhemoglobin