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Radioiodinated anti-TAG-72 CC49 tetravalent single-chain Fv antibody .


Cheng KT1.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2007 Jul 23 [updated 2008 Jan 22].

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National Center for Biotechnology Information, NLM, NIH, Bethesda, MD, Email:


Radioiodinated Anti-TAG-72 CC49 tetravalent single-chain Fv antibody (125I/131I-CC49 [sc(Fv)2]2 Ab), which is formed by the conjugation of 125I or 131I with a bioengineered recombinant anti–tumor-associated glycoprotein 72 (TAG-72) antibody construct, has been developed for gamma imaging of cancers that express TAG-72 (1, 2). 125I has a physical half-life (t½) of 60 days with a gamma energy that is not ideal for in vivo imaging. 131I has a physical half-life (t½) of 8.02 days with a gamma energy that is high but acceptable for in vivo imaging. The TAG-72 antigen was isolated from the LS-174T human colon cancer xenograft as a high molecular weight glycoprotein (molecular mass of 106 Da) with mucin-like characteristics (3-6). It is expressed on a variety of human adenocarcinomas such as pancreatic, breast, colorectal, prostate, endometrial, and ovarian cancers. This antigen has also been shown to be shed into the serum of cancer patients (7). The murine monoclonal antibody (MAb) B72.3 against TAG-72 was initially generated by immunization of mice with a membrane-enriched fraction of a human breast carcinoma (8). With the use of affinity-purified TAG-72 from LS-174T as an immunogen, CC49 and other anti–TAG-72 MAbs with higher affinity constants (Ka) have been produced and characterized (3, 4, 8, 9). Radiolabeled MAbs have been developed for both the diagnosis and treatment of tumors (10). Radiolabeled B72.3 and CC49 have shown excellent tumor localization capabilities with potential diagnostic and therapeutic applications in the clinical setting (11, 12). Because of their relatively large size, radiolabeled intact MAbs tend to have unfavorable imaging kinetics, poor tumor penetration, and high potential for human anti-mouse antibody response (9, 13-15). One approach to minimize these problems is reducing intact antibodies to antibody fragments such as F(ab’)2 and Fab’ (16). Another approach is the development of genetic engineering methods to obtain single-chain Fv constructs (scFv) and multivalent scFv constructs (9, 17, 18). These scFv constructs contain the variable regions of the light chain (VL) and heavy chain (VH) connected by a flexible linker. Colcher et al. (19) constructed the monomeric CC49 scFv Ab (~27 kDa), which selectively recognizes a unique sialyl-Tn epitope of TAG-72. The radioiodinated CC49 scFv appeared to clear rapidly from the blood with good tumor penetration (18, 20). To further improve the imaging kinetics, Pavlinkova et al. (20) constructed the high-affinity dimer CC49 sc(Fv)2 (~60 kDa). The radioiodinated CC49 sc(Fv)2 showed good stability and increased avidity in vivo compared with the radioiodinated CC49 scFv construct. Goel et al. (1) formed the tetravalent [sc(Fv)2]2 construct (~120 kDa) that exhibited four potentially active antigen-binding sites and showed improved in vitro binding properties. Radioiodinated CC49 [sc(Fv)2]2 (125I/131I-CC49 [sc(Fv)2]2) was studied and evaluated for potential cancer therapy and diagnosis.

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