Glypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma.
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ABSTRACT: Glypican-3 (GPC3) is a tumor associated antigen expressed by hepatocellular carcinoma (HCC) cells. This preclinical study evaluated the efficacy of a theranostic platform using a GPC3-targeting antibody ?GPC3 conjugated to zirconium-89 (89Zr) and yttrium-90 (90Y) to identify, treat, and assess treatment response in a murine model of HCC. A murine orthotopic xenograft model of HCC was generated. Animals were injected with 89Zr-labeled ?GPC3 and imaged with a small-animal positron emission/computerized tomography (PET/CT) imaging system (immuno-PET) before and 30 days after radioimmunotherapy (RIT) with 90Y-labeled ?GPC3. Serum alpha fetoprotein (AFP), a marker of tumor burden, was measured. Gross tumor volume (GTV) and SUVmax by immuno-PET was measured using fixed intensity threshold and manual segmentation methods. Immuno-PET GTV measurements reliably quantified tumor burden prior to RIT, strongly correlating with serum AFP (R2?=?0.90). Serum AFP was significantly lower 30 days after RIT in 90Y-?GPC3 treated animals compared to those untreated (p?=?0.01) or treated with non-radiolabeled ?GPC3 (p?=?0.02). Immuno-PET GTV measurements strongly correlated with tumor burden after RIT (R2?=?0.87), and GTV of animals treated with 90Y-?GPC3 was lower than in animals who did not receive treatment or were treated with non-radiolabeled ?GPC3, although this only trended toward statistical significance. A theranostic platform utilizing GPC3 targeted 89Zr and 90Y effectively imaged, treated, and assessed response after radioimmunotherapy in a GPC3-expressing HCC xenograft model.
SUBMITTER: Labadie KP
PROVIDER: S-EPMC7881163 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
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