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89 Zr- N-Succinyldesferrioxamine-bevacizumab

89 Zr- N-Succinyldesferrioxamine-bevacizumab

Kam Leung

PMID: 20641842

Abstract:

Vascular endothelial growth factor (VEGF) 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). VEGF121, VEGF165, and VEGF189 are the forms secreted by most cell types and are active as homodimers linked by disulfide bonds. VEGF121 does not bind to heparin like the 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 VEGF receptors (1).
VEGF is overexpressed in various tumor cells and tumor-associated endothelial cells (3). Inhibition of VEGF receptor 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 anti-cancer treatment protocols. Bevacizumab is a humanized antibody against VEGF-A. It binds to all VEGF isoforms. Bevacizumab is approved for clinical use in metastatic colon carcinoma and non-small cell lung cancer. Nagengast et al. (11) prepared 89Zr-N-succinyldesferrioxamine-bevacizumab (89Zr-bevacizumab) for imaging VEGF expression in nude mice bearing SKOV-3 human ovarian tumor xenografts.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42411958	Flt1 active human			Price

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