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Molecular Ultrasound Imaging Using a Targeted Contrast Agent for Assessing Early Tumor Response to Antiangiogenic Therapy
Author(s) -
Sorace Anna G.,
Saini Reshu,
Mahoney Marshall,
Hoyt Kenneth
Publication year - 2012
Publication title -
journal of ultrasound in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 91
eISSN - 1550-9613
pISSN - 0278-4297
DOI - 10.7863/jum.2012.31.10.1543
Subject(s) - medicine , microbubbles , bevacizumab , vascularity , angiogenesis , contrast enhanced ultrasound , antiangiogenic therapy , ultrasound , pathology , molecular imaging , targeted therapy , cancer , chemotherapy , radiology , in vivo , microbiology and biotechnology , biology
Objectives Contrast‐enhanced ultrasound (US) and targeted microbubbles have been shown to be advantageous for angiogenesis evaluation and disease staging in cancer. This study explored molecular US imaging of a multitargeted microbubble for assessing the early tumor response to antiangiogenic therapy. Methods Target receptor expression of 2LMP breast cancer cells was quantified by flow cytometric analysis and characterization established with antibodies against mouse α V β 3 ‐ integrin, P‐selectin, and vascular endothelial growth factor receptor 2. Tumor‐bearing mice (n = 15 per group) underwent contrast‐enhanced US imaging of multitargeted microbubbles. Microbubble accumulation was calculated by destruction‐replenishment techniques and time‐intensity curve analysis. On day 0, mice underwent baseline imaging. Next, therapy group mice were injected with a 0.2‐mg dose of bevacizumab, and controls received matched saline injections. Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the mice were euthanized and tumors excised. Histologic analysis of microvessel density and intratumoral necrosis was completed on tumor sections. Results On day 3 after bevacizumab dosing, a 71.8% change in tumor vasculature was shown between the therapy and control groups ( P = .01). The therapy group had a 15.4% decrease in tumor vascularity, whereas the control group had a 56.4% increase. Conclusions Molecular US imaging of angiogenic markers can detect the early tumor response to drug therapy.