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European Journal of Nuclear Medicine and Molecular Imaging

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11-02-2022 | Molecular Imaging | Original Article

GPC3-targeted immunoPET imaging of hepatocellular carcinomas

Authors: Shuxian An, Di Zhang, You Zhang, Cheng Wang, Liang Shi, Weijun Wei, Gang Huang, Jianjun Liu

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2022

Abstract

Purpose

Early detection of hepatocellular carcinoma (HCC) remains a clinical challenge. Glypican 3 (GPC3) is a proteoglycan highly specific for HCC and is a potential diagnostic and therapeutic target for HCC. This work aims to develop GPC3-targeted immuno-positron emission tomography (immunoPET) imaging strategies and to assess the diagnostic values in preclinical HCC models.

Methods

Flow cytometry was used to screen GPC3-positive HCC cell lines. The expression of GPC3 in HCCs was detected by immunohistochemistry on tissue microarray. A novel GPC3-specific single domain antibody (sdAb) was produced and labeled with gallium-68 (⁶⁸Ga, T_1/2 = 1.1 h) and fluorine-18 (¹⁸F, T_1/2 = 1.8 h) to develop radiotracers with different half-lives. The diagnostic efficacies of the developed probes (i.e., [⁶⁸Ga]Ga-NOTA-G2, [¹⁸F]F-G2, and [⁶⁸Ga]Ga-NOTA-ABDG2) were interrogated in preclinical HCC models bearing varying GPC3 levels.

Results

GPC3 was strongly expressed on HCC cell lines and patients with poorly differentiated HCC. [⁶⁸Ga]Ga-NOTA-G2 immunoPET imaging specifically delineated the subcutaneous HCC lesions, outperforming the traditional ¹⁸F-fluorodeoxyglucose PET and the nonspecific [⁶⁸Ga]Ga-NOTA-NbGFP immunoPET. ImmunoPET imaging with [¹⁸F]F-G2 also efficiently diagnosed the tumors with clarity. Moreover, the fusion of G2 to an albumin-binding domain (ABD) significantly increased the tumor uptake and decreased kidney accumulation of the radiotracer when compared to [⁶⁸Ga]Ga-NOTA-G2.

Conclusions

In the work, we successfully developed sdAb-derived GPC3-targeted immunoPET imaging strategies and characterized the superior diagnostic accuracies in preclinical HCC models. Furthermore, we synthesized a fusion protein ABDG2 with improved targeting and pharmacokinetic properties, serving as a promising candidate for developing radioimmunotherapy agents.

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Title: GPC3-targeted immunoPET imaging of hepatocellular carcinomas
Authors: Shuxian An
Di Zhang
You Zhang
Cheng Wang
Liang Shi
Weijun Wei
Gang Huang
Jianjun Liu
Publication date: 11-02-2022
Publisher: Springer Berlin Heidelberg
Keywords: Molecular Imaging
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-05723-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

GPC3-targeted immunoPET imaging of hepatocellular carcinomas

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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