A Molecular Imaging Paradigm to Rapidly Profile Response to Angiogenesis-directed Therapy in Small Animals
- 7 January 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Imaging & Biology
- Vol. 11 (3), 204-212
- https://doi.org/10.1007/s11307-008-0193-9
Abstract
Purpose The development of novel angiogenesis-directed therapeutics is hampered by the lack of non-invasive imaging metrics capable of assessing treatment response. We report the development and validation of a novel molecular imaging paradigm to rapidly assess response to angiogenesis-directed therapeutics in preclinical animal models. Procedures A monoclonal antibody-based optical imaging probe targeting vascular endothelial growth factor receptor-2 (VEGFR2) expression was synthesized and evaluated in vitro and in vivo via multispectral fluorescence imaging. Results The optical imaging agent demonstrated specificity for the target receptor in cultured endothelial cells and in vivo. The agent exhibited significant accumulation within 4T1 xenograft tumors. Mice bearing 4T1 xenografts and treated with sunitinib exhibited both tumor growth arrest and decreased accumulation of NIR800-αVEGFR2ab compared to untreated cohorts (p = 0.0021). Conclusions Molecular imaging of VEGFR2 expression is a promising non-invasive biomarker for assessing angiogenesis and evaluating the efficacy of angiogenesis-directed therapies.Keywords
This publication has 41 references indexed in Scilit:
- The biologic basis of in vivo angiogenesis imagingFrontiers in Bioscience-Landmark, 2007
- Radioiodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft modelNuclear Medicine and Biology, 2006
- In vitro and in vivo evaluation of [123I]-VEGF165 as a potential tumor markerNuclear Medicine and Biology, 2005
- Correlation of dynamic contrast enhancement MRI parameters with microvessel density and VEGF for assessment of angiogenesis in breast cancerJournal of Magnetic Resonance Imaging, 2003
- Molecular imaging in living subjects: seeing fundamental biological processes in a new lightGenes & Development, 2003
- Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial cellsOncogene, 2000
- Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cellsBiochemical and Biophysical Research Communications, 1989
- Induction of angiogenesis during the transition from hyperplasia to neoplasiaNature, 1989
- Tumor Angiogenesis: Therapeutic ImplicationsNew England Journal of Medicine, 1971
- ISOLATION OF A TUMOR FACTOR RESPONSIBLE FOR ANGIOGENESISThe Journal of Experimental Medicine, 1971