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18F-Labeled N-succinimidyl-4-fluorobenzoate–conjugated rat anti-mouse vascular endothelial growth factor receptor 2 monoclonal antibody linked to microbubbles.


Chopra A1.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2011 Nov 14 [updated 2012 Mar 15].

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National Center for Biotechnology Information, NLM, Bethesda, MD 20894


Microbubbles (MBs) are spherical shells that are made of various types of biocompatible materials, such as albumin, carbohydrates, lipids or polymers, and are filled with heavy gases (nitrogen, perfluorocarbon, or sulfur hexafluoride) in the core. In the clinic, MBs are commonly used for the noninvasive real-time imaging of inflammation, thrombus formation, and angiogenesis with ultrasonography (1, 2). The features and utility of MBs have been discussed recently by Postema and Gilja (3). Targeted MBs can be generated by coating the MB shells with small molecules, peptides, proteins, or antibodies (Abs) that have a high binding affinity for disease-specific molecular markers, such as αVβ3 integrins, endoglin, and the vascular endothelial growth factor receptor 2 (VEGFR2), which are expressed on the surface of endothelial cells (2). Because MBs are inexpensive, widely available, and easy to use, there is much interest in the preclinical development and evaluation of targeted MBs for the imaging of diseases related to the circulatory system (4). Investigators are particularly interested in targeting the VEGFR2 with MBs because, once activated, this receptor initiates several signal transduction pathways that influence the differentiation, mitogenic potential, and migration of the endothelial cells, and VEGFR2 is overexpressed in cancerous tumors to promote angiogenesis in the lesions. In addition, VEGFR2 is the target of several antiangiogenic drugs that have been approved by the United States Food and Drug Administration for the treatment of various cancers (e.g., bevacizumab, an anti-VEGFR2 Ab). It was shown in a preclinical study that MBs coated with a rat anti-mouse VEGFR2 Ab (Avas12a1 MBs) can be used with ultrasonography imaging to visualize tumor angiogenesis in mice, but the biodistribution of the targeted MBs was not investigated (5). However, it is important to study the biodistribution of a therapeutic drug or an imaging agent because such investigations are essential to determine the pharmacokinetics, nonspecific targets, and side effects of a drug or imaging agent. Therefore, in continuation of the earlier study (5), the biodistribution of 18F-labeled Avas12a1 MBs was investigated with dynamic micro-positron emission tomography (micro-PET) in mice bearing mouse angiosarcoma SVR cell tumors (2).

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