FDGPET found wanting in macrophage imaging of atherosclerosis
Novel molecular imaging detection of atherosclerosis is increasingly being presented to head off arterial damage and risk of cardiac events before they are found by more conventional methods, but FDGPET may not be the ideal solution, according to a study published July 25th in the Journal of Nuclear Medicine.
Sina Tavakoli, MD, from the department of radiology at the University of Texas Health Science Center in San Antonio, Texas, and colleagues evaluated divergent bioenergetics in metabolic imaging of atherosclerosis with F-18 FDG and found that aspects of macrophage polarization may be independent of glucose uptake.
Atherosclerosis is replete with monocyte-derived macrophages in major arteries. While the pathology of atherosclerosis has been found to be highly varied, all such variations can all lead to serious complications or sudden death, especially from the rupture of vulnerable plaques. While CT and myocardial perfusion imaging (MPI) are the workhorses of atherosclerotic imaging, these bring pathology to light only after arteries have advanced into the red zone of cardiovascular risk.
“Most acute myocardial events result from the rupture of plaques, which do not produce hemodynamically significant stenosis, further limiting the potential of conventional imaging techniques,” wrote Tavakoli et al. “These vulnerable plaques are rich in inflammatory cells, in particular macrophages, which contribute to plaque expansion and weakening of the supportive fibrous cap through expression of numerous cytokines, chemokines, and proteases predisposing the plaque to rupture. Therefore, there has been a growing interest in the development and validation of diagnostic approaches that specifically target ongoing cellular and molecular events occurring in the atherosclerotic vessel wall rather than assessment of their late consequences.”
For this animal study, researchers fed mice regular chow as a source of peritoneal macrophages for cell culture. Harvested cells were cultured for two days in the presence of the cellular medium RPMI-1640 and 10 percent fetal bovine serum, 2 mM GlutaMAX, nonessential amino acids, 1 mM sodium pyruvate, and a buffer of 20 mM N-(2-hydroxyethyl)piperazine-N9-(2-ethanesulfonic acid) with 50 ng/mL interferon-y in addition to 10 ng/mL of tumor necrosis factor-α or 10 ng/mL of lipopolysaccharide (LPS) or interleukin-4 to produce inflammatory phenotypes, M1, MLPS and M2 macrophage polarization. Results of the research revealed that MLPS alone, not M1 or M2 polarized macrophages, kicked up glucose uptake. In fact, LPS led to a 2.5 fold increase, indicating that glucose metabolism is regulated independently from states of polarization. This suggests that F-18 FDG may not be able to effectively image macrophage polarization.
“Our data demonstrate that enhanced glucose uptake is not an intrinsic feature of inflammatory activation of macrophages but appears to be induced by selected stimuli, such as LPS,” wrote the authors. “We also showed that M2 macrophage polarization induces mitochondrial biogenesis, resulting in the acquisition of a significant spare respiratory capacity, which may provide these cells with the necessary bioenergetic flexibility to survive for long periods in a hostile environment.”
Further research is necessary to gain a greater understanding of these bioenergetics and to evaluate other possible biomarkers for their ability to image the inflammatory response as it relates to the risk and development of atherosclerosis.