Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy

Abstract

Cancer immunotherapy is an evolving and promising cancer treatment that takes advantage of the body’s immune system to yield effective tumor elimination. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. However, despite impressive tumor effects and extended patient survival, only a small proportion of patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations, due to intrinsic tumor heterogeneity and the latter being invasive. In addition, the unique response patterns of these therapies are not adequately captured by conventional imaging modalities. Consequently, non-invasive, sensitive, and quantitative molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using specific radiotracers, have been increasingly used for longitudinal whole-body monitoring of immune responses. Immunotherapies rely on the effector function of CD8+ T cells and natural killer cells (NK) at tumor lesions; therefore, the monitoring of these cytotoxic immune cells is of value for therapy response assessment. Different immune cell targets have been investigated as surrogate markers of response to immunotherapy, which motivated the development of multiple imaging agents. In this review, the targets and radiotracers being investigated for monitoring the functional status of immune effector cells are summarized, and their use for imaging of immune-related responses are reviewed along their limitations and pitfalls, of which multiple have already been translated to the clinic. Finally, emerging effector immune cell imaging strategies and future directions are provided.

Translational immunology: Applying fundamental discoveries to human health and autoimmune diseases

“…Imaging techniques are also important tools for studying human immunology. Whole-body imaging, such as MRI, single photon computerized tomography (SPECT), positron emission tomography, and magnetic particle imaging, are being deployed to track immune cells in vivo [103][104][105]. Each of these modalities rely on labeling the immune cell of interest with a tracer for visualization.…”

“…Each of these modalities rely on labeling the immune cell of interest with a tracer for visualization. To date, most of this work in humans has focused on molecular imaging of cytotoxic T cells using lineage tracers to assess the response to CAR T-cell therapy or immune checkpoint inhibitor therapy in the setting of cancer [103,105]. Whole-body imaging has also been utilized in the setting of autoimmune disease but primarily in animal models.…”

Skin Cancer Pathobiology at a Glance: A Focus on Imaging Techniques and Their Potential for Improved Diagnosis and Surveillance in Clinical Cohorts

“…Therefore, it is becoming highly attractive to image these aspects of the TME to identify the mechanisms of immune evasion operative in each patient and guide the development of targeted therapeutic approaches that will increase the chances of therapeutic success in the affected patients [ 273 ]. To achieve this goal, several radiotracers have been developed to image interleukins [ 274 ] and specific immune cells, including B cells [ 275 ], NK cells [ 274 ], macrophages [ 276 ], myeloid cells [ 277 ], and T cells [ 278 ]. We are summarizing herein most recent evidence of immunoPET strategies in delineating T cells using immune checkpoint molecules, such as indoleamine 2,3-dioxygenase (IDO) and the PD-1/PD-L1 axis.…”