In vivo Imaging Technologies to Monitor the Immune System

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.

The Future of Cancer Diagnosis, Treatment and Surveillance: A Systemic Review on Immunotherapy and Immuno-PET Radiotracers

“…In particular, radionuclide-labeled immunoglobulins G (IgG) antibodies (mAbs), antibody fragments or small proteins may be used to detect in-vivo the expression of ICs (PD-L1, PD-1 and CTLA-4), and/or other key molecules of immune checkpoint pathways and immune responses through SPECT or PET/CT images [ 15 ]. The choice of the right antigen expressed only on target cells with the right radionuclide is fundamental to create a good radiotracer: [ 111 In], [ 89 Zr] and [ 64 Cu] with longer half-lives (67.2, 78.4 and 12.7 h, respectively) are better suited to label intact antibodies (mAbs), while [ 18 F] and [ 68 Ga] with shorter half-lives (109.8 and 67.7 min, respectively) are more suitable for labeling of smaller ligands, such as nanobodies or small proteins [ 48 , 54 ]. The key radionuclides used for the development of new radiotracers in the immunotherapy field are listed in Table 1 .…”

Imaging Assessment of Tumor Response in the Era of Immunotherapy

“…Therefore, by combining FDG-PET/CT with LAT1-PET/CT, immune response activity could be assessed by determining the difference between FDG (tumor viability and immune response) and LAT1 tracer accumulation (tu-mor viability). The other approach to distinguish tumor cells from immune response is the labeling of adoptive immune cells with radioisotopes [101]. Indeed, 111 In detectable by SPECT and 89 Zr detectable by PET have already been tested for immune cell labeling in CAR-T therapy [102].…”

Personalized radioiodine therapy for thyroid cancer patients with known disease

“…Pretherapeutic PET imaging with 18 F-FAZA or 18 F-FMISO (fluoromisonidazole, a marker of tissue hypoxia) allows us to identify patients in need of a radiosensitizer targeting tumor hypoxia and to evaluate the efficacy of the intervention. While imaging technologies that monitor the dynamics of the immune system are still under development, multiple imaging modalities and immunologic targets are being actively explored 15 . Anatomic imaging allows us to monitor changes in lesion volume and lesion volume doubling time such that the speed of disease progression and the extent of responsiveness to ongoing therapeutic intervention can be closely monitored to provide guidance on timely clinical intervention.…”