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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

08.01.2024 | Original Article

Platelet-derived growth factor receptor β-targeted positron emission tomography imaging for the noninvasive monitoring of liver fibrosis

verfasst von: Zhao Li, Hao Yang, Xin Li, Tianshan She, Ze Tao, Yi Zhong, Tao Su, Yanru Feng, Qiuxiao Shi, Lin Li, Rong Tian, Shisheng Wang, Jingqiu Cheng, Huawei Cai, Xiaofeng Lu

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 6/2024

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Abstract

Purpose

Noninvasive quantifying activated hepatic stellate cells (aHSCs) by molecular imaging is helpful for assessing disease progression and therapeutic responses of liver fibrosis. Our purpose is to develop platelet-derived growth factor receptor β (PDGFRβ)-targeted radioactive tracer for assessing liver fibrosis by positron emission tomography (PET) imaging of aHSCs.

Methods

Comparative transcriptomics, immunofluorescence staining and flow cytometry were used to evaluate PDGFRβ as biomarker for human aHSCs and determine the correlation of PDGFRβ with the severity of liver fibrosis. The high affinity affibody for PDGFRβ (Z_PDGFRβ) was labeled with gallium-68 (⁶⁸Ga) for PET imaging of mice with carbon tetrachloride (CCl₄)-induced liver fibrosis. Binding of the [⁶⁸Ga]Ga-labeled Z_PDGFRβ ([⁶⁸Ga]Ga-DOTA-Z_PDGFRβ) for aHSCs in human liver tissues was measured by autoradiography.

Results

PDGFRβ overexpressed in aHSCs was highly correlated with the severity of liver fibrosis in patients and CCl₄-treated mice. The ⁶⁸Ga-labeled Z_PDGFRβ affibody ([⁶⁸Ga]Ga-DOTA-Z_PDGFRβ) showed PDGFRβ-dependent binding to aHSCs. According to the PET imaging, hepatic uptake of [⁶⁸Ga]Ga-DOTA-Z_PDGFRβ increased with the accumulation of aHSCs and collagens in the fibrotic livers of mice. In contrast, hepatic uptake of [⁶⁸Ga]Ga-DOTA-Z_PDGFRβ decreased with spontaneous recovery or treatment of liver fibrosis, indicating that the progression and therapeutic responses of liver fibrosis in mice could be visualized by PDGFRβ-targeted PET imaging. [⁶⁸Ga]Ga-DOTA-Z_PDGFRβ also bound human aHSCs and visualized fibrosis in patient-derived liver tissues.

Conclusions

PDGFRβ is a reliable biomarker for both human and mouse aHSCs. PDGFRβ-targeted PET imaging could be used for noninvasive monitoring of liver fibrosis in mice and has great potential for clinical translation.

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Titel: Platelet-derived growth factor receptor β-targeted positron emission tomography imaging for the noninvasive monitoring of liver fibrosis
verfasst von: Zhao Li
Hao Yang
Xin Li
Tianshan She
Ze Tao
Yi Zhong
Tao Su
Yanru Feng
Qiuxiao Shi
Lin Li
Rong Tian
Shisheng Wang
Jingqiu Cheng
Huawei Cai
Xiaofeng Lu
Publikationsdatum: 08.01.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 6/2024
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06577-7

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Platelet-derived growth factor receptor β-targeted positron emission tomography imaging for the noninvasive monitoring of liver fibrosis

Abstract

Purpose

Methods

Results

Conclusions

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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