(18)F-DPA-714 PET Imaging for Detecting Neuroinflammation in Rats with Chronic Hepatic Encephalopathy

• Published in: Theranostics Vol. 6; no. 8; p. 1220
• Main Authors: Kong, Xiang, Luo, Song, Wu, Jin Rong, Wu, Shawn, De Cecco, Carlo N, Schoepf, U Joseph, Spandorfer, Adam J, Wang, Chun Yan, Tian, Ying, Chen, Hui Juan, Lu, Guang Ming, Yang, Gui Fen, Zhang, Long Jiang
• Format: Journal Article
• Language: English
• Published: Australia 2016
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Carrier Proteins - analysis; Chronic Disease; Disease Models, Animal; Fluorine Radioisotopes - administration & dosage; Fluorine Radioisotopes - pharmacokinetics; Hepatic Encephalopathy - diagnosis; Hepatic Encephalopathy - drug therapy; Ibuprofen - therapeutic use; Positron-Emission Tomography - methods; Pyrazoles - administration & dosage; Pyrazoles - pharmacokinetics; Pyrimidines - administration & dosage; Pyrimidines - pharmacokinetics; Rats; Receptors, GABA-A - analysis; Treatment Outcome; ibuprofen; positron emission tomography; neuroinflammation; hepatic encephalopathy
• DOI: 10.7150/thno.15362
• ISSN: 1838-7640

Neuroinflammation is considered to be the pathogenesis of hepatic encephalopathy (HE), and imaging neuroinflammation is implicated in HE management. (11)C-PK11195, a typical translocator protein (TSPO) radiotracer, is used for imaging neuroinflammation. However, it has inherent limitations, such as short half-life and limited availability. The purpose of this study was to demonstrate the efficiency of new generation TSPO radiotracer, (18)F-DPA-714, in detecting and monitoring neuroinflammation of chronic HE. This study was divided into two parts. The first part compared (18)F-DPA-714 and (11)C-PK11195 radiotracers in ten HE induced rats [bile duct ligation (BDL) and fed hyperammonemic diet (HD)] and 6 control rats. The animal subjects underwent dynamic positron emission tomography (PET) during 2-day intervals. The (11)C-PK11195 PET study showed no differences in whole brain average percent injected dose per gram (%ID/g) values at all time points (all P>0.05), while the (18)F-DPA-714 PET study showed higher whole brain average %ID/g values in HE rats compared to control group rats at 900 s to 3300 s after injecting radiotracer (all P<0.05). The second part of the study evaluated the effectiveness of ibuprofen (IBU) treatment to chronic HE. Forty rats were classified into six groups, including Sham+normal saline (NS), Sham+IBU, BDL+NS, BDL+HD+NS, BDL+IBU, and BDL+HD+IBU groups. (18)F-DPA-714 PET was used to image neuroinflammation. Whole and regional brain average %ID/g values, neurological features, inflammatory factors and activated microglia showed better in the IBU groups than in the NS groups (all P<0.05) and no difference was seen in the Sham groups compared to IBU groups (all P>0.05). In conclusion, this study demonstrated that (18)F-DPA-714 is an ideal TPSO radiotracer for imaging neuroinflammation and monitoring anti-neuroinflammation treatment efficacy of chronic HE.