Exploiting Glutamine Consumption in Atherosclerotic Lesions by Positron Emission Tomography Tracer (2 S,4 R)-4-18F-Fluoroglutamine

Front Immunol. 2022 Jan 25:13:821423. doi: 10.3389/fimmu.2022.821423. eCollection 2022.


Increased glutamine metabolism by macrophages is associated with development of atherosclerotic lesions. Positron emission tomography/computed tomography (PET/CT) with a glutamine analog (2S,4R)-4-18F-fluoroglutamine (18F-FGln) allows quantification of glutamine consumption in vivo. Here, we investigated uptake of 18F-FGln by atherosclerotic lesions in mice and compared the results with those obtained using the glucose analog 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG). Uptake of 18F-FGln and 18F-FDG by healthy control mice (C57BL/6JRj) and atherosclerotic low-density lipoprotein receptor-deficient mice expressing only apolipoprotein B100 (LDLR-/-ApoB100/100) was investigated. The mice were injected intravenously with 18F-FGln or 18F-FDG for in vivo PET/CT imaging. After sacrifice at 70 minutes post-injection, tracer uptake was analyzed by gamma counting of excised tissues and by autoradiography of aorta cryosections, together with histological and immunohistochemical analyses. We found that myocardial uptake of 18F-FGln was low. PET/CT detected lesions in the aortic arch, with a target-to-background ratio (SUVmax, aortic arch/SUVmean, blood) of 1.95 ± 0.42 (mean ± standard deviation). Gamma counting revealed that aortic uptake of 18F-FGln by LDLR-/-ApoB100/100 mice (standardized uptake value [SUV], 0.35 ± 0.06) was significantly higher than that by healthy controls (0.20 ± 0.08, P = 0.03). More detailed analysis by autoradiography revealed that the plaque-to-healthy vessel wall ratio of 18F-FGln (2.90 ± 0.42) was significantly higher than that of 18F-FDG (1.93 ± 0.22, P = 0.004). Immunohistochemical staining confirmed that 18F-FGln uptake in plaques co-localized with glutamine transporter SLC7A7-positive macrophages. Collectively these data show that the 18F-FGln PET tracer detects inflamed atherosclerotic lesions. Thus, exploiting glutamine consumption using 18F-FGln PET may have translational relevance for studying atherosclerotic inflammation.

Keywords: 18F-fluoroglutamine; PET/CT; atherosclerosis; inflammation; macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein B-100 / genetics
  • Atherosclerosis / diagnostic imaging*
  • Atherosclerosis / metabolism
  • Disease Models, Animal
  • Fluorodeoxyglucose F18
  • Glutamine / analogs & derivatives*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Positron Emission Tomography Computed Tomography*
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics


  • Apolipoprotein B-100
  • Receptors, LDL
  • Glutamine
  • Fluorodeoxyglucose F18