Noninvasive Imaging in Immunotherapy

A review of recent advances in the noninvasive imaging of immunotherapeutic targets.

In a review article published in Cancer Letters, authors recapped recent advances in the noninvasive imaging of immunotherapeutic targets, including immune checkpoint inhibitors, immune cells, and more. They also looked at future directions of the field including multimodal/multispectral imaging and radiomics.

“Molecular imaging, combined with disease-specific imaging probes can provide non-invasive, early and dynamic information about effects of immune cells or other cells in the tumor microenvironment (TME), as well as the target expression and the biodistribution of immunomodulatory drugs in the body, thereby allowing clinicians to predict which patients are most likely to benefit from immunotherapy,” wrote authors, led by Yang Du, CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Beijing.

Below are certain key points detailed in the review.

Imaging immune cells
The relationship between immune cells and tumor cells in the tumor microenvironment (TME) has come to the fore. Du et al. examined imaging of various cell types that are mobilized to the tumor microenvironment, including T cells, B cells, natural killer cells, macrophages, and dendritic cells. In the TEM, these cells influence tumor growth and exert antitherapeutic effects.

Noninvasive imaging for tracking T cells mostly involves indirect cell-labeling methods, such as labeling using intact antibodies, labeling using antibody fragments, labeling based on cell metabolism, and labeling based on reporter gene.

For tracking NK cells in vivo, molecular imaging strategies including optical imaging, magnetic resonance imaging, and positron emission tomography have been used.

Imaging PD-1
The efficacy of anti-PD-1 agents varies widely among different patients, thus new tracers and probes need to be designed to identify PD-1 expression in immunotherapy responsive patients.  Du et al. suggest that fluorescence optical imaging be utilized to track the distribution of probes in the body.

Imaging PD-L1
PD-L1 is found on the surface of tumor cells, T cells, B cells, and APCs. Blocking PD-L1 boosts T cell activity and yields immune-mediated tumor inhibition. The authors note that three-dimension optical imaging allows for cellular resolution.  CT plus anti-PD-L1 antibody-coated gold nanoparticles is currently a powerful technique to separate responders and nonresponders to anti-Pd-L1 antibody therapy.

Cancer vaccine imaging
Cancer vaccines are mostly made up of RNA, DNA, long peptide vaccines, viral vector vaccines, engineered bacteria, and antigen-loaded DC. Cancer vaccines have been tested in both preclinical and clinical research. Clearance efficacy of various delivery systems for peptide-based cancer vaccines have been analyzed using MRI.

Future directions
“Multimodal imaging combines the advantages of two or more imaging modalities to facilitate earlier and more sensitive diagnosis,” wrote the authors.

High-resolution anatomical data and molecular biologic data are combined in multimodal imaging. Molecular imaging and theranostic particles can be used to yield multimodal imaging techniques using NIRF, PET/SPECT, and MRI.

Furthermore, multispectral imaging plus semi-quantitative immunofluorescence techniques can visualize interactions between different populations of immune cells and tumor cells in the tumor microenvironment. This approach could proffer a more accurate elucidation of immunotherapy. 

“With progress in artificial intelligence and big data analysis, radiomics can be used to extract quantitative imaging features from clinical CT, PET, or MRI and offer a more comprehensive diagnostic approach, via the integration of genomics, molecular pathology, and clinical data, to uncover underlying cellular and molecular information,” concluded the authors.