Molecular imaging in gastric cancer: state-of-the-art techniques and emerging opportunities

Abstract Background Gastric cancer (GC) remains a major global health challenge with persistently poor survival rates, largely attributable to late-stage diagnosis and the inherent limitations of conventional imaging modalities, including CT, MRI, and FDG PET/CT, in detecting early lesions, identifying peritoneal metastases, and capturing tumor heterogeneity. There is a critical unmet need for non-invasive imaging approaches capable of visualizing GC-specific molecular biomarkers to enable more accurate diagnosis, risk stratification, and personalized treatment planning. Main body Molecular imaging integrates high-sensitivity tracer-based techniques with high-resolution anatomical imaging, allowing in vivo visualization of key biological processes and molecular targets in GC. This review provides a comprehensive overview of recent advances in molecular imaging platforms for GC, including PET, SPECT, molecular optical imaging, and molecular MRI. We summarize the biological rationale, imaging mechanisms, and emerging clinical relevance of representative molecular targets, such as HER2, PD-L1, CLDN18.2, FAP, VEGF, and Trop2. In addition, we discuss the development and application of diverse classes of imaging probes, including monoclonal antibodies, single-domain antibodies, affibodies, peptides, and nanomaterials, highlighting their roles in improving lesion detection, delineating intratumoral heterogeneity, guiding targeted and immune-based therapies, and supporting image-guided surgical and interventional procedures. Key challenges in clinical translation, including dynamic target expression, suboptimal pharmacokinetics, and the lack of standardized imaging protocols, are also critically examined. Conclusions Despite existing translational barriers, continued advances in probe engineering, chemical synthesis, and imaging instrumentation are rapidly expanding the clinical potential of molecular imaging in GC. These developments are expected to facilitate more precise diagnosis, treatment monitoring, and patient stratification, ultimately supporting the broader goals of precision oncology and personalized management of gastric cancer.