FDG shows immuno cell polarization in atherosclerotic inflammation

In an attempt to tease out the best possible technique for imaging the inflammation associated with atherosclerotic plaques, researchers peered into the cellular tangle and tested both FDG and MR imaging with ultrasmall superparamagnetic iron oxide particles (USPIO) to find out what kind of relationships were happening at the molecular level. Researchers found a complex interplay of macrophage heterogeneity and subtle genetic up and downregulation that hint at the pathology of atherosclerosis, according to a study published May 13 in the Journal of Nuclear Medicine.

Tomoko Satomi, from the metabolic disease drug discovery unit and division of pharmaceutical research at Takeda Pharmaceutical Company, Fujisawa, Japan, and colleagues, applied H-3 labeled FDG and USPIO and observed the level of macrophage M1 and M2 uptake, as well as the messenger RNA expressions of hexokinases and glucose transporters (GLUTs) implicated in glucose metabolism. The study also focused on glucose-6-phosphatase (G6Pase), which catalyzes hexokinase reverse reactions.

“We first investigated the association between macrophage polarization and FDG and USPIO accumulation using human THP-1 macrophages,” wrote Satomi et al. “Then, to elucidate the molecular mechanism of FDG and USPIO accumulation in polarized macrophages, we analyzed the expression of genes responsible for F-18 FDG uptake and metabolism and USPIO uptake and iron export.”

Results showed a polarization between M1 and M2. This interaction was seen to be associated with the atherosclerotic disease process. Researchers determined that M1 polarization led to an uptick in FDG accumulation and was more indicative of the inflammatory process compared to M2.

“The preferential uptake of FDG by M1 macrophages led to the hypothesis that M1 and M2 differed in the expression of the glucose uptake–related molecules because FDG is taken up by cells in a manner analogous to glucose,” the researchers wrote. “We observed that the mRNA expression of GLUT-1 and GLUT-3 was upregulated in M1 macrophages.”

GLUT-1 was markedly upregulated in M1 compared to M2 (P < 0.01 vs. P < 0.01), as was GLUT-3. Hexokinase expression in HK1 and HK2 were similarly upregulated. G6Pase was downregulated in M1 macrophages, P <0.01. These total effects of M1 polarization led to decreased intracellular USPIO.

“Compared with M2, proatherogenic M1 macrophages preferentially accumulated FDG but not USPIO, suggesting that FDG PET is a useful method for the detection of proinflammatory M1 macrophages,” the authors concluded.