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. 2025 Dec;53(1):59-70.
doi: 10.1007/s00259-025-07439-0. Epub 2025 Jul 15.

Advancements in non-invasive visualization of the immune checkpoint TIGIT: a systematic review

Susanne Lütje  1   2 , Laura Schäfer  3 , Betül Altunay  3 , Fabian Hertel  3 , Agnieszka Morgenroth  3 , Felix M Mottaghy  3   4   5
Affiliations

Advancements in non-invasive visualization of the immune checkpoint TIGIT: a systematic review

Susanne Lütje et al. Eur J Nucl Med Mol Imaging. 2025 Dec.

Abstract

Purpose: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a novel immune checkpoint receptor implicated in tumor immune evasion. Non-invasive imaging of TIGIT expression holds potential for improving patient selection and monitoring in cancer immunotherapy. This systematic review aims to evaluate recent advancements in radiotracer development for non-invasive visualization of TIGIT.

Methods: A comprehensive literature search was conducted up to February 2025 using databases including PubMed and Web of Science. The search terms "TIGIT imaging", "TIGIT PET", "TIGIT SPECT", and "TIGIT visualization" were used, focusing on those reporting on the development, characterization, or application of immuno-PET tracers targeting TIGIT expression. Both preclinical and clinical studies were reviewed.

Results: Six studies met the inclusion criteria, exploring tracers targeting TIGIT expression on immune cells. These studies have focused on the development of TIGIT-targeted imaging agents, including radiolabeled antibodies, peptides, and nanobodies for positron emission tomography (PET) and single-photon emission tomography (SPECT) imaging. These agents demonstrated high specificity and enabled visualization of TIGIT expression in preclinical models and one exploratory clinical study.

Conclusion: Novel radiotracers for non-invasive imaging of TIGIT show potential for enhancing personalized cancer immunotherapy. TIGIT-targeted imaging agents allow for the visualization and quantification of TIGIT expression in tumors/tumor microenvironment, which in future might contribute to better patient selection and treatment monitoring. Further research and clinical validation are necessary to optimize these imaging techniques for routine clinical application.

Keywords: Immune checkpoint; Immune targeting; PET/CT Imaging; TIGIT.

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Conflict of interest statement

Declarations. Ethics approval: Not applicable. Competing interests: Felix M. Mottaghy is medical advisor for NanoMab Technology Ltd. and Advanced Accelerator Applications (AAA) GmbH/Novartis and has recently received institutional grants from NanoMab Technology Ltd., Siemens, and GE Precision HealthCare LLC. He is also supported by the German Research Foundation (DFG) within the framework of the Research Training Group 2375 “Tumor-targeted Drug Delivery” (grant 331065168), the Clinical Research Unit CRU 5011 “Integrating emerging methods to advance translational kidney research (InteraKD)” (project 445703531). In addition, his research is funded by the German Federal Ministry of Research and Education (project 16GW0319K). Moreover, he is an editor in the European Journal of Nuclear Medicine and Molecular Imaging.

References

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