Positron Emission Tomography Imaging of Macrophages in Cancer

Abstract

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.

Predicting Survival in Patients with Pancreatic Cancer by Integrating Bone Marrow FDG Uptake and Radiomic Features of Primary Tumor in PET/CT

“…Therefore, immune suppression mediated by myeloid-derived suppressor cells might lead to poor prognosis of patients with increased FDG uptake of BM [ 17 ]. In addition, considering the significant positive correlation between the degree of FDG uptake and macrophage infiltration in the tumors, FDG uptake of BM could be affected by the metabolic activity of BM-derived macrophages [ 18 ]. BM-derived macrophages can convert to tumor-associated macrophages in the tumor microenvironment, which contributes to a favorable microenvironment for tumor growth [ 18 , 35 ].…”

“…In addition, considering the significant positive correlation between the degree of FDG uptake and macrophage infiltration in the tumors, FDG uptake of BM could be affected by the metabolic activity of BM-derived macrophages [ 18 ]. BM-derived macrophages can convert to tumor-associated macrophages in the tumor microenvironment, which contributes to a favorable microenvironment for tumor growth [ 18 , 35 ]. In previous studies, increased myeloid-derived suppressor cells and tumor-associated macrophages were also significantly associated with poor response to treatment and worse survival in patients with pancreatic cancer [ 8 , 35 , 36 , 37 ].…”

“…Since then, growing evidence has suggested that the host microenvironment plays an essential role in the growth and metastasis of cancer cells, as well as the biological characteristics of cancer cells [ 20 , 40 ]. Because immune cells derived from the BM such as myeloid-derived suppressor cells and macrophages significantly influence the host organ microenvironment, the degree of BM FDG uptake, which reflects the degree of production and metabolic activity of BM-derived immune cells, can be used to estimate the immune microenvironment of the host organ [ 17 , 18 , 35 , 41 ]. Hence, a prognostic model that combines tumor factors and BM imaging parameters that reflect host factors could improve the prediction of the prognosis of cancer patients when compared with a model only with tumor intrinsic factors.…”

“…Meanwhile, in contrast to studies that focused on imaging features of cancer lesions, other recent studies evaluated the degree of host inflammatory response to cancer using FDG PET/CT [ 15 , 16 ]. FDG uptake of bone marrow (BM) is known to be associated with the production of myeloid cells, including neutrophils and macrophages, and showed a significant correlation with the degree of the systemic inflammatory response of the host [ 15 , 16 , 17 , 18 ]. Furthermore, a number of studies have demonstrated the significant positive association between FDG uptake of BM and survival in diverse kinds of cancers [ 15 , 16 , 17 , 19 ].…”

Influences on PET Quantification and Interpretation

“…Further determinants of the biodistribution of various other radiopharmaceuticals are also beyond the scope of this article but have been addressed by previous reviews. These include physiological and pharmacological factors [ 31 ], the in vivo degradation of peptide-based PET radiopharmaceuticals [ 32 ], and interactions between the lesion microenvironment and radiopharmaceuticals [ 33 , 34 , 35 , 36 ].…”