Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, l -methionine, 67 Ga-citrate, and 125 I-HSA

Abstract

The purpose of this study was to evaluate the localization of positron emission tomography (PET) tracers [2-deoxy-2-fluoro-D-glucose (FDG), thymidine, and L-methionine] in sites of bacterial infection, and to contrast this with that of other tracers. The left calf muscles of rats were infected with a suspension of Escherichia coli and the biodistribution of 18F- or 3H-FDG, 3H-thymidine, L-11C- or 3H-methionine, gallium-67 citrate (67Ga-citrate) and iodine-125 human serum albumin (125I-HSA) was determined in these animals. 3H-FDG uptake in the infectious foci was evaluated by autoradiography of histological sections. Although 18F-FDG, 67Ga-citrate, and 125I-HSA showed comparatively high uptake in the infected muscle [the percentage activity of injected dose (ID) per gram of tissue normalized for rat weight in kilogram (%ID/g)xkg at 2 h postinjection was as follows: 18F-FDG, 0.184+/-0.026 to 0.218+/-0.046; 67Ga-citrate, 0.221+/-0.016; 125I-HSA, 0. 198+/-0.019], the infected muscle to blood ratio was much higher for 18F-FDG than for 67Ga-citrate or 125I-HSA (18F-FDG, 10.31+/-0.76 to 14.89+/-2.26; 67Ga-citrate, 1.24+/-0.67; 125I-HSA, 0.20+/-0.02). The draining reactive lymph nodes also showed higher accumulation of 18F-FDG than of 67Ga-citrate or 125I-HSA. The uptake of 3H-thymidine and L-11C- or 3H-methionine in the infected muscle was lower than that of 18F- or 3H-FDG (at 2 h postinjection, 3H-thymidine = 0. 039+/-0.005 and L-3H-methionine = 0.063+/-0.007 (%ID/g)xkg. Autoradiographs showed that the highest 3H-FDG uptake was seen in the area of inflammatory cell infiltration surrounding the necrotic region. In conclusion, 18F-FDG, which rapidly accumulates in sites of bacterial infection and in reactive lymph nodes with a high target to background ratio, appears to be a promising infection detection agent.

Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18F positron emission tomography

“…Initially the uptake of 18 F-FDG in atherosclerotic plaque was thought to be due to the respiratory burst of macrophages when phagocytizing the subendothelial oxidized LDL particles (38,39). However, Folco et al showed that hypoxia is the main driver that modulates glucose uptake in macrophages, mediated by increased expression of hexokinase-2 rather than upregulation of the GLUT1 transporter (40).…”

“…Both macrophages and foam cells have been shown in vitro to take up 18 F-FDG and at a comparable level to some cancer cell lines (34,36,37). Initially the uptake of 18 F-FDG in atherosclerotic plaque was thought to be due to the respiratory burst of macrophages when phagocytizing the subendothelial oxidized LDL particles (38,39).…”

“…However, there is now also increasing recognition of the scope for molecular imaging to provide assessment of the biological composition of plaque and characterize the dynamic nature of more vulnerable lesions. In this review, we will direct our focus to the use of positron emission tomography (PET) and the applicability of 18 Fluoride-based radionuclide tracers for molecular imaging of coronary atherosclerosis.…”

“…18 F-FDG PET was adopted rapidly for cancer imaging and was initially thought to potentially be a specific imaging modality that would allow not only monitoring of malignancy but also a tool to help differentiate it from other pathologies. However, this proved not to be the case, with 18 F-FDG uptake also seen in both benign conditions and in the setting of inflammation (15)(16)(17)(18).…”

“…Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18 but in the early stages of atherosclerosis these apoptotic cells are cleared by efferocytosis that has an anti-inflammatory and stabilizing effect. Over an extended period of time though the need for recurrent efferocytosis and prolonged exposure of cells within the plaque environment to oxidized low density lipoprotein (LDL) can lead to endoplasmic reticulum stress within macrophages and cause secondary necrosis, releasing their cellular contents and further stimulating the cycle and contributing to the formation of lipid rich plaques within the arterial wall (3)(4)(5).…”