Abstract
The inflammatory response, mediated by tissue-resident or newly recruited macrophages, is an underlying pathophysiological condition for many diseases, including diabetes, obesity, neurodegeneration, atherosclerosis, and cancer. Paradoxically, inflammation is a double-edged sword in oncology. Macrophages are, generally speaking, the major drivers of inflammatory insult. For many solid tumors, high density of cells expressing macrophage-associated markers have generally been found in association with a poor clinical outcome, characterized by inflamed microenvironment, a high level of dissemination and resistance to conventional chemotherapies. On another hand, radiation treatment also triggers an inflammatory response in tumors (often referred to as pseudoprogression), which can be associated with a positive treatment response. As such, non-invasive imaging of cancer inflammation and tumor-associated macrophages (TAMs) provides a revolutionary diagnostic tool and monitoring strategy for anti-inflammatory, immuno- and radiotherapies. Recently, quantitative T2-weighted magnetic resonance imaging (qT2wMRI), using injection of superparamagnetic iron oxide nanoparticles (SPIONs), has been reported for the assessment of TAMs non-invasively in animal models and in human trials. The SPIONs are magnetic resonance imaging (MRI) contrast agents that significantly decrease T2 MR relaxation times in inflamed tissues due to the macrophage-specific uptake and retention. It has been shown that macrophage-populated tumors and metastases will accumulate iron oxide nanoparticles and decrease T2-relaxation time that will result in a negative (dark) contrast in qT2wMRI. Non-invasive imaging of TAMs using SPION holds a great promise for staging the inflammatory microenvironment of primary and metastatic tumors as well monitoring the treatment response of cancer patients treated with radiation and immunotherapy.
Highlights
The tumor microenvironment subsidizes to tumor progression, invasion, metabolic reprograming, and resistance to therapy
tumor-associated macrophages (TAMs) can be recruited from circulating monocytes as a result of therapy-induced apoptosis resulting in tumor inflammation after, for example, radiation or chemotherapy
Radiation induces a genetic signature of chronic inflammation, which is enriched in genes regulating transendothelial migration, monocyte maturation, and leukocyte chemoattraction [35,36,37]
Summary
The tumor microenvironment subsidizes to tumor progression, invasion, metabolic reprograming, and resistance to therapy. Iron-based nanoparticles have been known as T2-weighted contrast for magnetic resonance imaging (MRI). The recent studies have shown that superparamagnetic iron oxide nanoparticles (SPIONs) have a potential for non-invasive T2-weighted MRI assessment on tissue residential macrophages, including TAMs [12]. This approach has a high-translational potential, since several of the existing SPION agents are approved in Europe for MR imaging and commercially available for human use. Ferumoxytol has superb magnetic properties and has been safely used in animal and human trials as an off-label MRI contrast agent [12, 14,15,16,17,18,19,20,21,22]
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