89Zr-αGPC3

89Zr-αGPC3 is a **radiopharmaceutical theranostic agent** consisting of a monoclonal antibody targeting glypican-3 (GPC3) conjugated to zirconium-89 (89Zr) via deferoxamine (DFO) chelator. GPC3 is a cell surface proteoglycan that is overexpressed in most hepatocellular carcinomas (HCC) but minimally expressed in normal liver tissue, making it an attractive target for HCC-specific imaging and therapy. The agent works through **antibody-dependent, antigen-specific binding** to GPC3-expressing tumor cells. When used for imaging, 89Zr-αGPC3 enables immuno-positron emission tomography (immunoPET) that can detect sub-centimeter liver tumors with high tumor-to-liver contrast ratios (up to 32.5). The radiopharmaceutical demonstrates peak tumor uptake of 836.6 ± 86.6 %ID/g compared to background liver uptake of 27.5 ± 1.6 %ID/g. As part of a theranostic platform, 89Zr-αGPC3 can be used sequentially with its therapeutic counterpart 90Y-αGPC3 (yttrium-90 labeled) for radioimmunotherapy. The imaging component allows for tumor staging, treatment planning, and assessment of treatment response. The therapeutic version (90Y-αGPC3) delivers cytotoxic radiation specifically to GPC3-expressing tumor cells, inducing apoptosis while sparing normal liver parenchyma. Both murine and humanized versions of the antibody have been developed, with the humanized version (89Zr-αGPC3H) showing comparable efficacy to the murine version while offering improved potential for clinical translation due to reduced immunogenicity.

Other names

Zirconium-89 labeled anti-GPC3 antibodyZirconium89 labeled anti-GPC3 antibodyZirconium 89 labeled anti-GPC3 antibody89Zr-labeled αGPC3