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Published on: November 14, 2025
Beyond expression: Molecular imaging of Claudin18.2 to decipher target accessibility and guide precision oncology
Yueling Deng1, Jinquan Han2, Xiao Zhang1
1Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Molecular Imaging, Wuhan 430022, China; Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan 430022, China.
Abstract:
Claudin18.2 (CLDN18.2) has emerged as a clinically important therapeutic target in gastrointestinal malignancies following the success of zolbetuximab-based therapy. However, unlike conventional overexpression-driven biomarkers, the clinical relevance of CLDN18.2 is fundamentally shaped by target accessibility rather than expression alone. Physiologically concealed within gastric epithelial tight junctions, CLDN18.2 becomes exposed during malignant transformation, creating a spatially heterogeneous and dynamically accessible target landscape. This exposure-dependent biology challenges conventional tissue-based assessment and provides a strong rationale for molecular imaging. Recent advances in CLDN18.2-targeted molecular imaging across antibody, engineered-fragment, and nanobody platforms have enabled noninvasive whole-body assessment of target accessibility and lesion-level heterogeneity beyond localized biopsy. Importantly, imaging signals reflect not only antigen expression, but also probe-dependent pharmacokinetics, tissue penetration, and microenvironmental accessibility. In this review, we discuss the biological basis of CLDN18.2 accessibility, summarize emerging imaging and theranostic strategies, and examine the evolving role of molecular imaging in patient stratification and imaging-informed precision oncology.
Insights
Claudin18.2 (CLDN18.2) is a key target in GI cancers. Molecular imaging reveals CLDN18.2 accessibility, crucial for effective patient selection and treatment beyond simple expression levels.
Area of Science:
- Oncology
- Molecular Imaging
- Biomarker Discovery
Background:
- Claudin18.2 (CLDN18.2) is a significant therapeutic target in gastrointestinal malignancies.
- Its clinical utility depends on target accessibility, not just expression levels, as it's exposed during malignant transformation.
Purpose of the Study:
- To review the biological basis of CLDN18.2 accessibility.
- To summarize emerging molecular imaging and theranostic strategies for CLDN18.2.
- To examine the role of molecular imaging in patient stratification for precision oncology.
Main Methods:
- Review of recent advances in CLDN18.2-targeted molecular imaging platforms (antibody, engineered-fragment, nanobody).
- Discussion of noninvasive whole-body assessment of target accessibility and heterogeneity.
- Analysis of factors influencing imaging signals: antigen expression, pharmacokinetics, tissue penetration, and microenvironmental accessibility.
Main Results:
- Molecular imaging enables noninvasive assessment of CLDN18.2 accessibility and heterogeneity.
- Imaging signals integrate expression with probe and tissue-specific factors.
- Emerging theranostic strategies leverage these imaging advances.
Conclusions:
- CLDN18.2 accessibility is a critical determinant of therapeutic success in gastrointestinal cancers.
- Molecular imaging offers a powerful tool for assessing CLDN18.2 landscape beyond traditional methods.
- Imaging-informed strategies are vital for precision oncology and patient stratification.
