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86Y-CHX-A''-Diethylenetriamine pentaacetic acid-bevacizumab.


Leung K1.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2010 Dec 17 [updated 2011 Mar 16].

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National Center for Biotechnology Information, NLM, NIH


The vascular endothelial growth factor (VEGF) family is composed of five VEGF glycoproteins (VEGF-A, VEGF-B, VEGF-C, VEGF-D, and VEGF-E) and consists of at least six isoforms of various numbers of amino acids (121, 145, 165, 183, 189, and 206 amino acids) produced through alternative splicing (1). VEGF-A is composed of VEGF121, VEGF165, and VEGF189 isoforms, which are secreted by most cell types and are active as homodimers linked by disulfide bonds. VEGF121 does not bind to heparin like other VEGF species do (2). VEGF is a potent angiogenic factor that induces proliferation, sprouting, migration, and tube formation of endothelial cells. There are three high-affinity tyrosine kinase VEGF receptors (VEGFR-1, Flt-1; VEGFR-2, KDR/Flt-1; and VEGFR-3, Flt-4) on endothelial cells. Several types of non-endothelial cells, such as hematopoietic stem cells, melanoma cells, monocytes, osteoblasts, and pancreatic β cells, also express VEGFRs (1). VEGF is overexpressed in various tumor cells and tumor-associated endothelial cells (3). Inhibition of VEGFR function has been shown to inhibit pathological angiogenesis as well as tumor growth and metastasis (4, 5). Radiolabeled VEGF has been developed as a single-photon emission computed tomography tracer for imaging solid tumors and angiogenesis in humans (6-8). However, several studies have shown that cancer treatments (photodynamic therapy, radiotherapy, and chemotherapy) can lead to increased tumor VEGF expression and subsequently to more aggressive disease (9, 10). Therefore, it is important to measure VEGF levels in the tumors to design better anticancer treatment protocols. Bevacizumab is a humanized antibody against VEGF-A (11) that binds to all VEGF-A isoforms. Bevacizumab is approved for clinical use in metastatic colon carcinoma and non-small cell lung cancer (12). VEGFR-2 has been shown to mediate most of the VEGF-A activation in tumor endothelial cells (13, 14). Nayak et al. (15) prepared 86Y-CHX-A''-diethylenetriamine pentaacetic acid-bevacizumab (86Y-CHX-A''-DTPA-bevacizumab) for imaging VEGF expression in nude mice bearing SKOV-3 human ovarian tumor xenografts.

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