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68Ga-Labeled anti-EpCAM diabody against epithelial cell adhesion molecule.


Leung K1.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2010 Aug 06 [updated 2010 Nov 19].

Author information

National for Biotechnology Information, NLM, NIH, Bethesda, MD


Epithelial cell adhesion molecules (EpCAM) are found on the cell surface of epithelial cells of many epithelial tissues such as the pancreas, jejunum, colon, kidney, salivary gland, and prostate (1). EpCAM is responsible for intracellular signaling and polarity, and it mediates cell differentiation, proliferation, migration, and adhesion (2, 3). It is a pan-epithelial differentiation antigen that is expressed on almost all carcinomas (4). Approximately 70% of human prostate cancers show high levels of EpCAM expression (5, 6). 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 (7). 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) has been evaluated for targeting in several tumor antigen systems and has demonstrated rapid tumor localization and high-contrast imaging (7, 8). In particular, human IgG42 anti-EpCAM (clone 42 (huIgG42), ~150kDa) was isolated from a human naïve antibody library. The monomeric scFv4218 (clone 42 with 18 amino acid linker), dimeric scFv429 (diabody), and trimeric scFv420 (tribody) were genetically constructed. These fragments retain excellent EpCAM-binding properties (dissociation constant (Kd) = 0.24–11.8 nM) and were developed as EpCAM imaging agents. They were conjugated with the bifunctional chelating agent N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC) to enable labeling with 68Ga for imaging of EpCAM expression in solid tumors (9).

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