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.

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Molecular Imaging and Biology Pub Date : 2024-11-21 DOI:10.1007/s11307-024-01967-1

Min-Jeong Kim, 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 min 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: 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 [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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通过大鼠关节炎和爪水肿模型探索 (2S,4R)-4-[18F]fluoroglutamine 作为炎症新代谢成像标记物的潜在用途。

目的：(2S,4R)-4-[18F]氟谷氨酰胺（[18F]FGln）是一种很有前景的癌症代谢成像标记物。基于主要炎症细胞与癌细胞一样严重依赖谷氨酰胺代谢这一事实，我们在卡拉胶诱导的爪水肿（CIPE）和胶原诱导的关节炎（CIA）两种大鼠模型中探索了[18F]FGln作为炎症代谢成像标记物的潜在用途：CIPE模型（n = 4）是在PET前三小时向左后爪注射200 µL的3%卡拉胶溶液。CIA模型（n = 4）是在PET前3-4周在尾基部皮下注射200微克胶原蛋白乳液而产生的。采用定性评分系统评估爪部炎症的严重程度。CT扫描后，通过尾静脉注射15.7 ± 4.9 MBq的[18F]FGln，然后在异氟烷麻醉下进行90分钟的动态显微PET扫描。在每个爪子中放置一个感兴趣体积，测量[18F]FGln的标准摄取值。CIPE模型大鼠未注射的右后爪作为两种模型的对照组。PET 测试后，对患有 CIA 的鼠爪进行病理学检查：结果：CIPE 模型显示，与未注射的爪子相比，注射爪子的摄取率呈上升趋势（P = 0.068）。在 CIA 模型中，有严重炎症的爪的摄取量明显高于对照组（P = 0.011），而有轻微炎症和无炎症的爪的摄取量分别略高（33%）和略低（-7%）。综合来看，CIA的[18F]FGln摄取量与炎症严重程度呈显著正相关（r = 0.88，P = 0.009）。病理结果证实，CIA 存在严重的炎症：结论：[18F]FGln摄取量在急性和慢性炎症中均有增加，且摄取水平与炎症严重程度呈显著正相关，这表明[18F]FGln有可能成为炎症的新型代谢成像标记物。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.