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89Zr-N-Succinyldesferal-chimeric monoclonal antibody G250.

Authors

Leung K.

Source

Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2010 Apr 22 [updated 2010 May 27].

Excerpt

In a variety of solid tumors, hypoxia was found to lead to tumor progression and the resistance of tumors to chemotherapy and radiotherapy (1-3). Tumor oxygenation is heterogeneously distributed within human tumors (4). Hypoxia in malignant tumors is thought to be a major factor limiting the efficacy of chemotherapy and radiotherapy. It would be beneficial to assess tumor oxygenation before and after therapy to provide an evaluation of tumor response to treatment and an insight into new therapeutic treatments (5). Tumor oxygenation is measured invasively using computerized polarographic oxygen-sensitive electrodes, which is regarded as the gold standard (6). Functional and non-invasive imaging of intratumoral hypoxia has been demonstrated to be feasible for the measurement of tumor oxygenation (7). Chapman proposed the use of 2-nitroimidazoles for hypoxia imaging (8). 2-Nitroimidazole compounds are postulated to undergo reduction in hypoxic condition, forming highly reactive oxygen radicals that subsequently bind covalently to macromolecules inside the cells (9). [18F]Fluoromisonidazole ([18F]FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia (7). Carbonic anhydrase (CA) IX is one of the most overexpressed genes in cells under hypoxic conditions (10). It is a transmembrane glycoprotein with CA activity in the extracellular domain, and it is found to be overexpressed in renal cell, cervical, lung, and colorectal tumors. Murine monoclonal antibody G250 against CA IX has been developed for in vitro and in vivo localization of CA IX in cells (11-13). G250 is found to bind to >94% of human clear-cell renal carcinoma. A murine-human chimeric G250 (cG250) has been generated to be less immunogenic in humans. 124I-cG250 has been evaluated as a PET imaging agent for renal cell carcinoma in mice (14) and patients (15). Brouwers et al. (16) explored the use of a 89Zr positron emitter (half-life, 3.27 days) to radiolabel cG250. 89Zr was conjugated to a bifunctional derivative of desferrioxamine B (Df) to cG250 for PET imaging of CA IX expression in tumors. 89Zr-Df-cG250 has been evaluated as a PET imaging agent for renal cell carcinoma in rats.

PMID:
20641994
[PubMed]
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