Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models

Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herei...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Li Wen, Lei Xia, Xiaoyi Guo, Hai-Feng Huang, Feng Wang, Xian-teng Yang, Zhi Yang, Hua Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	trastuzumab dMNPs PET/MRI imaging HER2 micro-PET/CT imaging Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c5ebd269418a4283b83e09e44815b3ff
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c5ebd269418a4283b83e09e44815b3ff
record_format	dspace
spelling	oai:doaj.org-article:c5ebd269418a4283b83e09e44815b3ff2021-11-17T04:31:02ZMultimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models2234-943X10.3389/fonc.2021.778728https://doaj.org/article/c5ebd269418a4283b83e09e44815b3ff2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.778728/fullhttps://doaj.org/toc/2234-943XTrastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herein, we constructed novel organic dopamine–melanin nanoparticles (dMNs) as a carrier and then surface-loaded them with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenograft (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specifically target the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs. 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, micro-PET/CT and PET/MRI showed that the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs as carrier (1.63 ± 0.07 vs. 0.90 ± 0.04 at 24 h, P = 0.002), a similarity found in 64Cu-labeled Her-PEG-dMNPs. Because 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the further evaluation of 124I-Her-PEG-dMNPs. Furthermore, immunohistochemistry staining confirmed the overexpression of HER2 in the animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.Li WenLi WenLei XiaXiaoyi GuoHai-Feng HuangFeng WangXian-teng YangXian-teng YangZhi YangZhi YangHua ZhuHua ZhuFrontiers Media S.A.articletrastuzumabdMNPsPET/MRI imagingHER2micro-PET/CT imagingNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	trastuzumab dMNPs PET/MRI imaging HER2 micro-PET/CT imaging Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	trastuzumab dMNPs PET/MRI imaging HER2 micro-PET/CT imaging Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Li Wen Li Wen Lei Xia Xiaoyi Guo Hai-Feng Huang Feng Wang Xian-teng Yang Xian-teng Yang Zhi Yang Zhi Yang Hua Zhu Hua Zhu Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models
description	Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herein, we constructed novel organic dopamine–melanin nanoparticles (dMNs) as a carrier and then surface-loaded them with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenograft (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specifically target the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs. 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, micro-PET/CT and PET/MRI showed that the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs as carrier (1.63 ± 0.07 vs. 0.90 ± 0.04 at 24 h, P = 0.002), a similarity found in 64Cu-labeled Her-PEG-dMNPs. Because 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the further evaluation of 124I-Her-PEG-dMNPs. Furthermore, immunohistochemistry staining confirmed the overexpression of HER2 in the animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.
format	article
author	Li Wen Li Wen Lei Xia Xiaoyi Guo Hai-Feng Huang Feng Wang Xian-teng Yang Xian-teng Yang Zhi Yang Zhi Yang Hua Zhu Hua Zhu
author_facet	Li Wen Li Wen Lei Xia Xiaoyi Guo Hai-Feng Huang Feng Wang Xian-teng Yang Xian-teng Yang Zhi Yang Zhi Yang Hua Zhu Hua Zhu
author_sort	Li Wen
title	Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models
title_short	Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models
title_full	Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models
title_fullStr	Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models
title_full_unstemmed	Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models
title_sort	multimodal imaging technology effectively monitors her2 expression in tumors using trastuzumab-coupled organic nanoparticles in patient-derived xenograft mice models
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c5ebd269418a4283b83e09e44815b3ff
work_keys_str_mv	AT liwen multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT liwen multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT leixia multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT xiaoyiguo multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT haifenghuang multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT fengwang multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT xiantengyang multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT xiantengyang multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT zhiyang multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT zhiyang multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT huazhu multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels AT huazhu multimodalimagingtechnologyeffectivelymonitorsher2expressionintumorsusingtrastuzumabcoupledorganicnanoparticlesinpatientderivedxenograftmicemodels
_version_	1718426016244826112

Multimodal Imaging Technology Effectively Monitors HER2 Expression in Tumors Using Trastuzumab-Coupled Organic Nanoparticles in Patient-Derived Xenograft Mice Models

Ejemplares similares