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

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 αGPC3 conjugated to zirconium-89 (89Zr) and yttrium-90 (90Y) to identify, treat, and ass...

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Autores principales:	Kevin P. Labadie, Andrew D. Ludwig, Adrienne L. Lehnert, Donald K. Hamlin, Aimee L. Kenoyer, Kevin M. Sullivan, Sara K. Daniel, Tara N. Mihailovic, Jonathan G. Sham, Johnnie J. Orozco, Raymond S. Yeung, Delphine L. Chen, D. Scott Wilbur, Robert S. Miyaoka, James O. Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ddea22e7449b4b418c2f02ca24983fd2
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spelling	oai:doaj.org-article:ddea22e7449b4b418c2f02ca24983fd22021-12-02T14:27:02ZGlypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma10.1038/s41598-021-82172-w2045-2322https://doaj.org/article/ddea22e7449b4b418c2f02ca24983fd22021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82172-whttps://doaj.org/toc/2045-2322Abstract 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 (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 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 90Y-labeled αGPC3. 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 (R 2 = 0.90). Serum AFP was significantly lower 30 days after RIT in 90Y-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 90Y-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 89Zr and 90Y effectively imaged, treated, and assessed response after radioimmunotherapy in a GPC3-expressing HCC xenograft model.Kevin P. LabadieAndrew D. LudwigAdrienne L. LehnertDonald K. HamlinAimee L. KenoyerKevin M. SullivanSara K. DanielTara N. MihailovicJonathan G. ShamJohnnie J. OrozcoRaymond S. YeungDelphine L. ChenD. Scott WilburRobert S. MiyaokaJames O. ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kevin P. Labadie Andrew D. Ludwig Adrienne L. Lehnert Donald K. Hamlin Aimee L. Kenoyer Kevin M. Sullivan Sara K. Daniel Tara N. Mihailovic Jonathan G. Sham Johnnie J. Orozco Raymond S. Yeung Delphine L. Chen D. Scott Wilbur Robert S. Miyaoka James O. Park Glypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma
description	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 αGPC3 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 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 90Y-labeled αGPC3. 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 (R 2 = 0.90). Serum AFP was significantly lower 30 days after RIT in 90Y-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 90Y-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 89Zr and 90Y effectively imaged, treated, and assessed response after radioimmunotherapy in a GPC3-expressing HCC xenograft model.
format	article
author	Kevin P. Labadie Andrew D. Ludwig Adrienne L. Lehnert Donald K. Hamlin Aimee L. Kenoyer Kevin M. Sullivan Sara K. Daniel Tara N. Mihailovic Jonathan G. Sham Johnnie J. Orozco Raymond S. Yeung Delphine L. Chen D. Scott Wilbur Robert S. Miyaoka James O. Park
author_facet	Kevin P. Labadie Andrew D. Ludwig Adrienne L. Lehnert Donald K. Hamlin Aimee L. Kenoyer Kevin M. Sullivan Sara K. Daniel Tara N. Mihailovic Jonathan G. Sham Johnnie J. Orozco Raymond S. Yeung Delphine L. Chen D. Scott Wilbur Robert S. Miyaoka James O. Park
author_sort	Kevin P. Labadie
title	Glypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma
title_short	Glypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma
title_full	Glypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma
title_fullStr	Glypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma
title_full_unstemmed	Glypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma
title_sort	glypican-3 targeted delivery of 89zr and 90y as a theranostic radionuclide platform for hepatocellular carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ddea22e7449b4b418c2f02ca24983fd2
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Glypican-3 targeted delivery of 89Zr and 90Y as a theranostic radionuclide platform for hepatocellular carcinoma

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