Advances in PD-L1 Targeted Molecular Imaging Radiotracers Research: From Preclinical Exploration to Clinical Application.

Programmed death-ligand 1 (PD-L1) is highly expressed in tumour cells and the tumour microenvironment, mediates tumour immune evasion, and is a key target for cancer immunotherapy. Immunohistochemistry (IHC), as a conventional method for PD-L1 detection, has limitations such as invasiveness, temporal and spatial heterogeneity, and an inability to provide dynamic monitoring. In contrast, PD-L1-targeted molecular imaging enables non-invasive, quantitative, and whole-body visual assessment of PD-L1 expression, offering a precise tool for patient selection, treatment response prediction and dynamic monitoring in immunotherapy, and has thus become a focal point in precision oncology research. This paper systematically reviews the development trajectory of PD-L1-targeting radiotracers, including monoclonal antibodies, peptides, nanobodies, aptamers and small molecules. It summarises the targeting performance, pharmacokinetics, imaging efficacy and safety in preclinical and clinical studies; compares the advantages and suitable applications of different types of tracers; analyses the challenges currently facing the field, such as the lack of evaluation standards, tumour heterogeneity, insufficient clinical translation and a scarcity of multicentre data; and offers a prospect on the standardisation of PD-L1-targeted molecular imaging, the integration of diagnosis and treatment, multimodal imaging and its promotion and application in primary care settings. To date, more than 40 PD-L1-targeting tracers have undergone preclinical or clinical validation, with non-invasive imaging demonstrated to be feasible in over 100 cancer patients; early data support further in-depth research and clinical translation in this field.