The potential utility of (2S,4R)-4-[18F] fluoroglutamine as a novel metabolic imaging marker for inflammation explored by rat models of arthritis and paw edema.
Kim Min-Jeong, Hari K Akula, Jocelyn Marden, Kaixuan Li, Bao Hu, Paul Vaska, Wenchao Qu
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Abstract
Purpose: (2S,4R)-4-[18F]fluoroglutamine ([18F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent on glutamine metabolism like cancer cells, we explored the potential utility of [18F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA).
Procedures: The CIPE model (n = 4) was generated by injecting 200 μL of 3% carrageenan solution into the left hind paw three hours before the PET. The CIA model (n = 4) was generated by injecting 200 μg of collagen emulsion subcutaneously at the tail base 3-4 weeks before the PET. A qualitative scoring system was used to assess the severity of paw inflammation. After a CT scan, 15.7 ± 4.9 MBq of [18F]FGln was injected via the tail vein, followed by a dynamic micro-PET scan for 90 minutes under anesthesia with isoflurane. The standard uptake value of [18F]FGln was measured by placing a volume of interest in each paw. The non-injected right hind paws of the CIPE model rats served as controls for both models. The paws with CIA were pathologically examined after PET.
Results: In CIPE models, uptake in the injected paw was higher compared to the non-injected paw by 52-83%. In CIA models, uptake in the paws with severe inflammation was higher than the averaged controls by 54-173%, while that with mild and no inflammation was slightly higher (33%) and lower (-7%), respectively. Combined overall, the [18F]FGln uptake in CIA showed a significant positive correlation with inflammation severity (r = 0.88, P = 0.009). The pathological findings confirmed profound inflammation in CIA.
Conclusions: [18F]FGln uptake was increased in both acute and chronic inflammation, and the uptake level was significantly correlated with the severity, suggesting its potential utility as a novel metabolic imaging marker for inflammation.
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