Abstract
Simple SummaryTumor-associated macrophages (TAMs) play numerous roles in cancer biology and are an important component of the relationship between immune system response and tumor progression. Several new immunotherapy techniques have been developed that target TAMs and are under investigation in both clinical and preclinical settings. Despite this surge of new immunotherapy techniques, a means to specifically and quantifiably measure the presence of TAMs to ensure the viability of these therapies, has yet to be widely investigated. The development of molecular imaging agents that target TAMs provides a path to noninvasively gain valuable insight into the molecular and functional characteristics of the tumor microenvironment and how the immune response facilitates the progression of cancer or therapy response. This article reviews published preclinical and clinical research in the imaging of TAMs through Positron Emission Tomography (PET).Macrophages are large phagocytic cells that can be classified as a type of white blood cell and may be either mobile or stationary in tissues. The presence of macrophages in essentially every major disease makes them attractive candidates to serve as therapeutic targets and diagnostic biomarkers. Macrophages that are found in the microenvironment of solid tumors are referred to as tumor-associated macrophages (TAMs) and have been shown to influence chemoresistance, immune regulation, tumor initiation and tumor growth. The imaging of TAMs through Positron Emission Tomography (PET) has the potential to provide valuable information on cancer biology, tumor progression, and response to therapy. This review will highlight the versatility of macrophage imaging in cancer through the use of PET.
Highlights
The year 1883 marked the beginning of an exciting new era for immunology
This study provided the earliest description of macrophages and opened up a new field of research as numerous scientists propelled the field forward by working to advance current knowledge and understanding of the role of macrophages in many disease states [1,2]
Macrophages that are found in the microenvironment of solid tumors are referred to as tumor-associated macrophages (TAMs)
Summary
Metchnikoff introduced the concept of macrophages by determining phagocytes functions as a critical host-defense mechanism. Patients with stage I and II non-small cell lung cancer were enrolled in the study and 98 biopsy samples were collected: 48 adenocarcinomas and 50 squamous cell carcinomas These patients were imaged with [18 F]FDG-PET and immunohistochemistry was conducted for TAMs by using CD68 antibodies to differentiate between tumors with low CD68 and high CD68 levels. Xavier and colleagues continued their research with the utilization of single-domain antibody fragments to target CD206 with PET imaging, in hopes of measuring the presence of protumorigenic TAMs, in a recent study published in 2019 [45] They optimized their previous PET probe from their 2015 study to incorporate gallium-68 instead of fluorine to make it more translatable to clinical evaluation when considering the precedence that Keyaerts and colleagues created with their phase I study of a gallium-68 nanobody for PET/CT assessment of HER2 expression in breast carcinoma [46]. This group plans to initiate a phase I clinical trial with trial with [68Ga]Ga-NOTA-anti-MMR-sdAb in [45]
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