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76Br-Human recombinant anti-ED-B fibronectin L19-small immunoprotein.

Authors

The MICAD Research Team.

Source

Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2007 Aug 04 [updated 2007 Aug 27].

Excerpt

The 76Br-human recombinant anti-ED-B fibronectin L19-small immunoprotein (76Br-L19-SIP) is a radiolabeled molecular imaging agent developed for positron emission tomography (PET) imaging of tumor angiogenesis and guidance for antiangiogenic treatment (1). 76Br is a positron emitter with a 54% abundance and a half-life (t½) of 16.2 h. Angiogenesis is a process of development and growth of new blood vessels from pre-existing vessels (2). Tumor growth depends on the formation of new blood vessels from this process. Normal angiogenesis is orderly and highly regulated, whereas tumor angiogenesis is chaotic and irregular. Abnormal angiogenesis is important in the carcinogenesis, growth, and progression of solid and hematologic tumors in humans (3). Fibronectins (FNs) are a family of universal cell-adhesion molecules that are widely distributed (4). FN is a polymorphic glycoprotein of ~2,500 amino acids and has a high molecular mass of 250–280 kDa. FN occurs in soluble form in plasma and other body fluids and in insoluble form in the extracellular matrices (5, 6). Both forms are dimers composed of a series of repeating units of three types and joined by two disulfide bonds at the C-terminus of the molecule. FN polymorphism arises from alternative splicing patterns of the pre-mRNA or post-translational modifications of FN itself (6). The splice variant ED-B FN is highly expressed during angiogenesis in both neoplastic and normal tissues (7), but higher levels of ED-B expression have been found in primary and metastatic tumors in breast, colorectal, and non-small cell lung cancers (4, 8-10). Molecular imaging of angiogenesis offers serial non-invasive evaluation of both location and growth dynamics of tumors (11). PET or single-photon emission computed tomography imaging with an appropriate radiolabeled tracer targeted to angiogenic pathways may allow the evaluation of specific aspects of tumor vascular biology (10). A molecular probe that targets ED-B FN can be both an early tumor marker and a tool to monitor the success of antiangiogenic cancer therapy. The human recombinant single-chain antibody fragment (scFv) L19, which has a high affinity for ED-B FN, was developed by Pini et al. (12). Borsi et al (13). used the variable regions of L19 to construct a bivalent human SIP by fusing two scFvs to the ЄCH4 domain of the secretory isoform S2 of human IgE (Єs2−CH4). The Єs2−CH4 domain provides a covalent stabilization of the dimer (molecular mass = ~80 kDa) (14). This group of researchers and Tijink et al (15) prepared radioiodinated L19-SIP that showed specific accumulation around tumor neovasculature and tumor stroma with high ED-B expression. In an effort to develop a PET molecular probe, Rossin et al. (1) used enzymatic radiobromination to prepare 76Br-L19-SIP and performed biodistribution and PET imaging studies in mice bearing the mouse embryonal teratocarcinoma F9. 76Br has relatively favorable production and photon yieldsand 76Br has a sufficiently long physical t½ for PET imaging up to 48 h after injection.

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