Kim Min-Jeong, Hari K Akula, Jocelyn Marden, Kaixuan Li, Bao Hu, Paul Vaska, Wenchao Qu
{"title":"通过大鼠关节炎和爪水肿模型探索 (2S,4R)-4-[18F]fluoroglutamine 作为炎症代谢成像标记物的潜在用途。","authors":"Kim Min-Jeong, Hari K Akula, Jocelyn Marden, Kaixuan Li, Bao Hu, Paul Vaska, Wenchao Qu","doi":"10.21203/rs.3.rs-4493375/v1","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>(<i>2S,4R</i>)-4-[<sup>18</sup>F]fluoroglutamine ([<sup>18</sup>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 [<sup>18</sup>F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA).</p><p><strong>Procedures: </strong>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 [<sup>18</sup>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 [<sup>18</sup>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.</p><p><strong>Results: </strong>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 [<sup>18</sup>F]FGln uptake in CIA showed a significant positive correlation with inflammation severity (<i>r</i> = 0.88, <i>P</i> = 0.009). The pathological findings confirmed profound inflammation in CIA.</p><p><strong>Conclusions: </strong>[<sup>18</sup>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.</p>","PeriodicalId":94282,"journal":{"name":"Research square","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213212/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Kim Min-Jeong, Hari K Akula, Jocelyn Marden, Kaixuan Li, Bao Hu, Paul Vaska, Wenchao Qu\",\"doi\":\"10.21203/rs.3.rs-4493375/v1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>(<i>2S,4R</i>)-4-[<sup>18</sup>F]fluoroglutamine ([<sup>18</sup>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 [<sup>18</sup>F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA).</p><p><strong>Procedures: </strong>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 [<sup>18</sup>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 [<sup>18</sup>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.</p><p><strong>Results: </strong>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 [<sup>18</sup>F]FGln uptake in CIA showed a significant positive correlation with inflammation severity (<i>r</i> = 0.88, <i>P</i> = 0.009). The pathological findings confirmed profound inflammation in CIA.</p><p><strong>Conclusions: </strong>[<sup>18</sup>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.</p>\",\"PeriodicalId\":94282,\"journal\":{\"name\":\"Research square\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213212/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Research square\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.21203/rs.3.rs-4493375/v1\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research square","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21203/rs.3.rs-4493375/v1","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.
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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