Noninvasive Imaging of Cancer Immunotherapy

Abstract

Immunotherapy has revolutionized the treatment of several malignancies. Notwithstanding the encouraging results, many patients do not respond to treatments. Evaluation of the efficacy of treatments is challenging and robust methods to predict the response to treatment are not yet available. The outcome of immunotherapy results from changes that treatment evokes in the tumor immune landscape. Therefore, a better understanding of the dynamics of immune cells that infiltrate into the tumor microenvironment may fundamentally help in addressing this challenge and provide tools to assess or even predict the response. Noninvasive imaging approaches, such as PET and SPECT that provide whole-body images are currently seen as the most promising tools that can shed light on the events happening in tumors in response to treatment. Such tools can provide critical information that can be used to make informed clinical decisions. Here, we review recent developments in the field of noninvasive cancer imaging with a focus on immunotherapeutics and nuclear imaging technologies and will discuss how the field can move forward to address the challenges that remain unresolved.

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

“…Here, immune cells are isolated from a patient and incubated with the radionuclide ex-vivo, despite the high fragility (short viability) of the re-injected cells and only preclinical data available, till now. An in-vivo approach would allow the possibility of PET imaging at any time after cell infusion, especially this could be of particular interest in the case of CAR T cell infusion, allowing to verify their arrival and accumulation in the tumor and metastases rather than a simple assessment of their presence in the peripheral blood by serial sampling, as per current procedural lines [ 48 ]. The first trials were carried out using SPECT radionuclides, such as [ 99m Tc] labeled hexamethylpropyleneamine (HMPAO) or [ 111 In] labeled 8-hydroxy-quinoline (oxine).…”

“…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 .…”

Molecular Imaging in Immunotherapy: A Systematic Review

“…Here, immune cells are isolated from a patient and incubated with the radionuclide ex-vivo, despite the high fragility (short viability) of the re-injected cells and only preclinical data available, till now. An in-vivo approach would allow the possibility of PET imaging at any time after cell infusion, especially this could be of particular interest in the case of CAR T cell infusion, allowing to verify their arrival and accumulation in the tumor and metastases rather than a simple assessment of their presence in the peripheral blood by serial sampling, as per current procedural lines [46]. The first trials were carried out using SPECT radionuclides, such as [ 99m Tc] labeled hexamethylpropyleneamine (HMPAO) or [ 111 In] labeled 8hydroxy-quinoline (oxine).…”

“…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 [46,52]. The key radionuclides used for the development of new radiotracers in the immunotherapy field are listed in Table 1.…”

Nanobodies for Medical Imaging: About Ready for Prime Time?

“…Fluorine-18 ( 18 F) is a commonly used PET radioisotope with a short half-life (t 1/2 of ~110 min) and high specific activity [ 9 ]. Small molecules, such as fluorodeoxyglucose [ 18 F]FDG and fluorothymidine [ 18 F]FLT, are commonly used PET tracers [ 11 , 12 , 13 ]. Metabolically active, glucose-avid cells, such as fast-proliferating cancer cells and, to some extent, activated immune cells, demonstrate high uptake of the administered [ 18 F]FDG radiotracer.…”