Molecular Immune Targeted Imaging of Tumor Microenvironment

Abstract

Novel targeted therapies are rapidly emerging for the treatment of cancer. With the advent of new immune targeting agents, understanding the changes in the tumor microenvironment (TME) is critical. Given the complexity and several cellular mechanisms and factors that play a role in the TME, novel imaging methods to assess and evaluate the dynamic changes in the TME during treatment are needed. Several techniques are being developed for imaging TME including optical, fluorescence and photoacoustic methods. Positron emission tomography (PET) imaging can be used to track the dynamics of different molecular targets in the TME in live animals and in humans. Several novel PET imaging probes including radiolabeled antibodies, antibody fragments, and small molecules have been developed with many more that are under development preclinically and in early human studies. This review is a brief overview of some of the PET agents that are either in the preclinical developmental phase or undergoing early clinical studies.

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

“…PD-L1 targeting imaging agents mainly include 89 Zr-atezolizumab, 89 Zr-durvalumab, and 18 F-BMS-986192, all of which have been in clinical trials ( 95 ). Researchers uncovered that 89 Zr-atezolizumab uptake performed better than IHC or RNA sequencing-based predictive biomarkers in evaluating clinical responses for ICIs ( 96 ).…”

Reporter Genes for Brain Imaging Using MRI, SPECT and PET

“…Despite of many undergoing clinical trials and some now licensed for clinical use, the safety, accuracy, and efficiency of these therapies remain big concerns [ 91 , 92 ]. In vivo imaging tools are in urgent need for the longitudinal monitoring of the biological distribution and fate of these exogenous cells, genes, and viruses, as well as an evaluation of the therapeutic response and promotion of their clinical translation [ 91 , 93 ]. As one of the most promising approaches, reporter genes feature a high level of cellular specificity, without signal dilution, such as cellular proliferation or tumor metastasis.…”

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

“…1 The inhibitors nivolumab and pembrolizumab for the PD-1 immune checkpoint have been approved for the treatment of melanoma and other indications, and atezolizumab has been approved by the FDA as a PD-L1 inhibitor for the treatment of urothelial carcinoma. 2 However, low response rates, 3 limited therapeutic targets, and immune-related adverse events point to the importance of the development of new immune checkpoints.…”

“…Small-molecule imaging agents have good tissue penetrance and permeation compared to antibody-based tracers, but high uptake in the kidneys and bladder due to rapid metabolism and excretion makes them challenging to use as imaging agents to assess the immune response to cancer. Whereas, antibody-based PET imaging tracers allow highly specific targeted imaging of immune processes . Therefore, in the present study, a new antibody for TIM3 targeting was developed, and a 124 I-C23 probe was generated by 124 I nuclide labeling for TIM3 imaging in vitro and in vivo , which demonstrated the application potential of TIM3-targeting radiotracers in identifying patients who may benefit from immunotherapy and guiding immunotherapy efficacy and prognosis prediction.…”