The Potential Utility of (2S,4R)-4-[F]fluoroglutamine as a Novel Metabolic Imaging Marker for Inflammation Explored by Rat Models of Arthritis and Paw Edema.

PURPOSE

(2S,4R)-4-[F]fluoroglutamine ([F]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 [F]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 [F]FGln was injected via the tail vein, followed by a dynamic micro-PET scan for 90 min under anesthesia with isoflurane. The standard uptake value of [F]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

The CIPE models showed a trend toward higher uptake in the injected paw compared to the non-injected paw (P = 0.068). In CIA models, uptake in the paws with severe inflammation was significantly higher than the controls (P = 0.011), while that with mild and no inflammation was slightly higher (33%) and lower (-7%), respectively. Combined overall, the [F]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

[F]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.