(2S,4R)-4-[18F]氟谷氨酰胺作为关节炎和爪水肿大鼠模型探索的炎症的新型代谢成像标记物的潜在用途。
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.
发表日期:2024 Jun 20
作者:
Kim Min-Jeong, Hari K Akula, Jocelyn Marden, Kaixuan Li, Bao Hu, Paul Vaska, Wenchao Qu
来源:
Arthritis & Rheumatology
摘要:
目的 ( 2S,4R )-4-[ 18 F]氟谷氨酰胺 ([ 18 F]FGln) 是一种有前途的癌症代谢成像标记物。基于主要炎症细胞像癌细胞一样严重依赖谷氨酰胺代谢的事实,我们在两种大鼠模型中探索了 [ 18 F]FGln 作为炎症代谢成像标记物的潜在用途:角叉菜胶诱导的爪水肿 (CIPE) 和胶原诱发的关节炎(CIA)。程序:在 PET 前 3 小时将 200 µL 3% 角叉菜胶溶液注射到左后爪中,生成 CIPE 模型(n = 4)。 CIA模型(n = 4)是通过在PET前3-4周在尾基部皮下注射200μg胶原乳液来生成的。使用定性评分系统来评估爪子炎症的严重程度。 CT扫描后,通过尾静脉注射15.7±4.9MBq的[ 18 F]FGln,随后在异氟烷麻醉下进行90分钟的动态微型PET扫描。 [ 18 F]FGln 的标准摄取值通过在每只爪子中放置感兴趣的体积来测量。 CIPE 模型大鼠的未注射右后爪作为两个模型的对照。 PET 后对 CIA 的爪子进行病理检查。结果在 CIPE 模型中,注射爪子的吸收量比未注射爪子高 52-83%。在 CIA 模型中,严重炎症的爪子的摄取量比平均对照组高 54-173%,而轻度炎症和无炎症的爪子的摄取量分别略高 (33%) 和较低 (-7%)。总体而言,CIA中的[ 18 F]FGln摄取与炎症严重程度呈显着正相关(r = 0.88,P = 0.009)。病理结果证实了 CIA 的严重炎症。结论 [ 18 F]FGln 摄取在急性和慢性炎症中均增加,且摄取水平与严重程度显着相关,表明其作为新型炎症代谢成像标志物的潜在用途。
Purpose ( 2S,4R )-4-[ 18 F]fluoroglutamine ([ 18 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 [ 18 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 [ 18 F]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 [ 18 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 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 [ 18 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 [ 18 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.