PET/CT molecular imaging in the era of immune-checkpoint inhibitors therapy

Abstract

Cancer immunotherapy, especially immune-checkpoint inhibitors (ICIs), has paved a new way for the treatment of many types of malignancies, particularly advanced-stage cancers. Accumulating evidence suggests that as a molecular imaging modality, positron emission tomography/computed tomography (PET/CT) can play a vital role in the management of ICIs therapy by using different molecular probes and metabolic parameters. In this review, we will provide a comprehensive overview of the clinical data to support the importance of 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) imaging in the treatment of ICIs, including the evaluation of the tumor microenvironment, discovery of immune-related adverse events, evaluation of therapeutic efficacy, and prediction of therapeutic prognosis. We also discuss perspectives on the development direction of 18F-FDG PET/CT imaging, with a particular emphasis on possible challenges in the future. In addition, we summarize the researches on novel PET molecular probes that are expected to potentially promote the precise application of ICIs.

The development process of ‘fit-for-purpose’ imaging biomarkers to characterize the tumor microenvironment

“…Imaging BMs such as the transfer coefficient K trans for perfusion, the apparent diffusion coefficient for tumor cellularity measured by MRI, or measures of tumor glucose consumption using [ 18 F]FDG PET can be relevant to the TME. These imaging BMs, when properly applied are already ‘fit-for-purpose’ for application in early-phase clinical trials, but are not particularly specific for immunotherapy ( 23 , 24 ).…”

Construction and Preclinical Evaluation of 124I/125I-Labeled Antibody Targeting T Cell Immunoglobulin and Mucin Domain-3

“…10 Positron emission tomography (PET)/computed tomography (CT) can be used for noninvasive and dynamic whole-body scanning with different tracers to predict the response to ICIs therapy and guide drug delivery strategies by reflecting the expression of biomarkers in vivo. 11 The physical half-life of 124 I (t 1/2 = 100.2 h) is similar to the time needed for monoclonal antibody metabolism in vivo and has been extensively studied in both experimental and clinical immuno-PET. The method of labeling antibodies with 124 I is simple and retains good radiolabeling chemistry, so antibody drugs do not lose immunobiological activity.…”

Gallium-68-Labeled ZPDGFRβ Affibody: A Potential PET Probe for Platelet-Derived Growth Factor Receptor β-Expressing Carcinomas

“…Positron emission tomography (PET), as a radionuclide imaging technique, offers superior sensitivity, spatial resolution, temporal resolution, and quantification accuracy in the visualization of tumor lesions and microenvironments as well as the prognosis of patients with good responses to certain targeted therapies . Currently, there is an increasing interest in using small organic molecules, antibodies, and peptides for PET as a modality for imaging .…”

“…Positron emission tomography (PET), as a radionuclide imaging technique, offers superior sensitivity, spatial resolution, temporal resolution, and quantification accuracy in the visualization of tumor lesions and microenvironments as well as the prognosis of patients with good responses to certain targeted therapies. 11 Currently, there is an increasing interest in using small organic molecules, antibodies, and peptides for PET as a modality for imaging. 12 Affibody molecules are a new class of engineered affinity proteins with a molecular weight of 6.5 kDa that are constructed on the basis of a 58-amino acid residue protein domain from one of the IgG-binding domains of staphylococcal protein A.…”