Potential PET tracers for imaging of tumor-associated macrophages

Abstract

The increasing incidence of cancer over the years is one of the most challenging problems in healthcare. As cancer progresses, the recruitment of several immune cells is triggered. Infiltration of tumor-associated macrophages (TAMs) is correlated with poor patient prognosis. Since TAMs constitute a big portion of the tumor mass, targeting these cells seems to be an attractive approach for cancer immunotherapy. Additionally, TAM assessment using non-invasive imaging techniques, such as positron emission tomography (PET), might provide a better understanding of the role of TAMs in cancer, and a means for tumor profile characterization, patient selection for individualized immunotherapy and treatment monitoring. Imaging of TAMs using PET tracers is still in its infancy. TAMs have several characteristics that could be exploited as potential targets for imaging. Various PET tracers for these TAM biomarkers have been developed, although often in the context of (neuro)inflammatory diseases rather than cancer. Since macrophages in inflammatory diseases express similar biomarkers as TAMs, these PET tracers could potentially also be applied for the assessment of TAMs in the tumor microenvironment. Therefore, the present review provides an overview of the TAM biomarkers, for which potential PET tracers are available and discusses the status of these tracers.

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.…”

Targeting Tumor-Associated Macrophages for Imaging

“…TAM-targeting PET nanoprobes are typically constructed by a radionuclide-labeled molecule and a TAM-targeting vehicle. Some receptors mainly expressed by TAMs, such as the colony-stimulating factor 1 receptor (CSF-1R), CD206, scavenger receptors, chemokine (C–C motif) ligand 2 (CCL2), glucan receptor, folate receptors and arginase, usually become the targets of TAM-targeting PET nanoprobes [ 48 ]. As a novel imaging nanoprobe with a certain amount of mannose to maximize TAM-targeting ability, Man(6)-Alb is serum albumin containing six mannose molecules created by the click reaction ( Figure 6 a) [ 49 ].…”

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

“…Considering the growing importance of TAMs as an alternative strategy for future targeted radionuclide therapy, the article entitled ‘Potential PET tracers for imaging of tumor‑associated macrophages’ (Fernandes et al 2022 ) is of significant value as it provides an excellent overview of the status of the TAM biomarkers, for which potential PET-tracers are already available and under active preclinical and clinical evaluation.…”