Glypican-3 targeted delivery of 89 Zr and 90 Y as a theranostic radionuclide platform for hepatocellular carcinoma.

Autor: Labadie KP; Department of Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356410, Health Sciences Bldg. Room BB-442, Seattle, WA, 98195-6410, USA., Ludwig AD; Department of Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356410, Health Sciences Bldg. Room BB-442, Seattle, WA, 98195-6410, USA., Lehnert AL; Department of Radiology, University of Washington, Seattle, WA, USA., Hamlin DK; Department of Radiology, University of Washington, Seattle, WA, USA.; Department of Radiation Oncology, University of Washington, Seattle, WA, USA., Kenoyer AL; Clinical Research Division, Fred Hutch Cancer Research Center, Seattle, WA, USA., Sullivan KM; Department of Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356410, Health Sciences Bldg. Room BB-442, Seattle, WA, 98195-6410, USA., Daniel SK; Department of Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356410, Health Sciences Bldg. Room BB-442, Seattle, WA, 98195-6410, USA., Mihailovic TN; Department of Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356410, Health Sciences Bldg. Room BB-442, Seattle, WA, 98195-6410, USA., Sham JG; Department of Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356410, Health Sciences Bldg. Room BB-442, Seattle, WA, 98195-6410, USA., Orozco JJ; Clinical Research Division, Fred Hutch Cancer Research Center, Seattle, WA, USA., Yeung RS; Department of Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356410, Health Sciences Bldg. Room BB-442, Seattle, WA, 98195-6410, USA., Chen DL; Department of Radiology, University of Washington, Seattle, WA, USA., Wilbur DS; Department of Radiology, University of Washington, Seattle, WA, USA.; Department of Radiation Oncology, University of Washington, Seattle, WA, USA., Miyaoka RS; Department of Radiology, University of Washington, Seattle, WA, USA., Park JO; Department of Surgery, University of Washington Medical Center, 1959 NE Pacific Street, Box 356410, Health Sciences Bldg. Room BB-442, Seattle, WA, 98195-6410, USA. jopark@uw.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Feb 12; Vol. 11 (1), pp. 3731. Date of Electronic Publication: 2021 Feb 12.
DOI: 10.1038/s41598-021-82172-w
Abstrakt: 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 αGPC3 conjugated to zirconium-89 ( 89 Zr) and yttrium-90 ( 90 Y) 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 89 Zr-labeled αGPC3 and imaged with a small-animal positron emission/computerized tomography (PET/CT) imaging system (immuno-PET) before and 30 days after radioimmunotherapy (RIT) with 90 Y-labeled αGPC3. Serum alpha fetoprotein (AFP), a marker of tumor burden, was measured. Gross tumor volume (GTV) and SUV max 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 (R 2  = 0.90). Serum AFP was significantly lower 30 days after RIT in 90 Y-αGPC3 treated animals compared to those untreated (p = 0.01) or treated with non-radiolabeled αGPC3 (p = 0.02). Immuno-PET GTV measurements strongly correlated with tumor burden after RIT (R 2  = 0.87), and GTV of animals treated with 90 Y-αGPC3 was lower than in animals who did not receive treatment or were treated with non-radiolabeled αGPC3, although this only trended toward statistical significance. A theranostic platform utilizing GPC3 targeted 89 Zr and 90 Y effectively imaged, treated, and assessed response after radioimmunotherapy in a GPC3-expressing HCC xenograft model.
Databáze: MEDLINE
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