Abstract
The past two decades have brought impressive advancements in immune modulation, particularly with the advent of both cancer immunotherapy and biologic therapeutics for inflammatory conditions. However, the dynamic nature of the immune response often complicates the assessment of therapeutic outcomes. Innovative imaging technologies are designed to bridge this gap and allow non-invasive visualization of immune cell presence and/or function in real time. A variety of anatomical and molecular imaging modalities have been applied for this purpose, with each option providing specific advantages and drawbacks. Anatomical methods including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound provide sharp tissue resolution, which can be further enhanced with contrast agents, including super paramagnetic ions (for MRI) or nanobubbles (for ultrasound). Conjugation of the contrast material to an antibody allows for specific targeting of a cell population or protein of interest. Protein platforms including antibodies, cytokines, and receptor ligands are also popular choices as molecular imaging agents for positron emission tomography (PET), single-photon emission computerized tomography (SPECT), scintigraphy, and optical imaging. These tracers are tagged with either a radioisotope or fluorescent molecule for detection of the target. During the design process for immune-monitoring imaging tracers, it is important to consider any potential downstream physiologic impact. Antibodies may deplete the target cell population, trigger or inhibit receptor signaling, or neutralize the normal function(s) of soluble proteins. Alternatively, the use of cytokines or other ligands as tracers may stimulate their respective signaling pathways, even in low concentrations. As in vivo immune imaging is still in its infancy, this review aims to describe the modalities and immunologic targets that have thus far been explored, with the goal of promoting and guiding the future development and application of novel imaging technologies.
Highlights
The immune system and its functions are complex and dynamic, and imaging provides a unique opportunity to non-invasively monitor these processes in vivo
Each of the discussed imaging approaches bears a distinct mix of advantages and complications, necessitating careful selection of both target and modality
Parallel testing with control tracers can help indicate the extent of these off-target uptake phenomena, such as enhanced permeability and retention (EPR) effect commonly detected in tumors
Summary
The immune system and its functions are complex and dynamic, and imaging provides a unique opportunity to non-invasively monitor these processes in vivo. There are a variety of human conditions and diseases that could benefit from immunoimaging. Current cancer immunotherapies are designed to either directly target specific tumor-associated antigens, modulate components of immune activation, or suppress signaling pathways to enhance immune activity. Responders often show durable disease control, most patients fail to exhibit any benefit. Treatment efficacy is assessed through tumor volume measurements, post-treatment tissue biopsies, or peripheral blood assays, each of which have their limitations. Changes in tumor size may prove misleading, as an influx of helpful immune cells to the microenvironment often contribute
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