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Radioiodinated T84.66 minibody.

Authors

Leung K.

Source

Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2008 Feb 02 [updated 2008 Apr 03].

Excerpt

Carcinoembryonic antigen (CEA) was first identified from extracts of human colon adenocarcinoma (1) and fetal gut (2). It is a β-glycoprotein, and its predominant expression on the cell surface is increased in a variety of carcinomas and in certain inflammatory conditions such as inflammatory bowel disease (3, 4). CEA has a molecular weight of ~180 kDa, and it can be shed and detected in the serum (5). CEA expression is observed in patients with various carcinomas of the colon, lungs, thyroid, uterus, ovaries, pancreas, and medullary thyroid (6). Radiolabeled monoclonal antibodies (mAbs) have been developed for both the diagnosis and treatment of tumors (7, 8). 99mTc-Arcitumomab, a murine anti-CEA mAb Fab’ fragment, was developed for use in single-photon emission computed tomography (SPECT) imaging of CEA expression. Single-chain variable fragments (scFvs) of antibodies with a molecular mass of 25 kDa are cleared very rapidly from the circulation, but they exhibit poor tumor retention because they have a lower affinity than the parent antibody (9). On the other hand, bivalent antibody fragments possess more ideal tumor-targeting characteristics, including rapid tissue penetration, high target retention, and rapid blood clearance. The diabody fragment (a dimer of scFvs; molecular mass = 55 kDa) and the minibody fragment (a dimer of scFvs-CH3 with a linker comprising 18 amino acids; molecular mass = 80 kDa) of a murine/human chimeric anti-CEA T84.66 antibody have been evaluated for targeting in several tumor antigen systems with rapid tumor localization and high-contrast imaging (9, 10). In particular, murine/human chimeric anti-CEA T84.66 antibodies, which retain excellent CEA-binding properties (dissociation constant = 0.01–0.6 nM) (11-13), were developed as CEA imaging agents. A T84.66 minibody was radiolabeled with 124I and 123I for localization of CEA-positive tumors in mice and humans, respectively (14, 15).

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