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(18)F-DPA-714 PET Imaging for Detecting Neuroinflammation in Rats with Chronic Hepatic Encephalopathy.
- Source :
-
Theranostics [Theranostics] 2016 May 24; Vol. 6 (8), pp. 1220-31. Date of Electronic Publication: 2016 May 24 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- 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.
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Carrier Proteins analysis
Chronic Disease
Disease Models, Animal
Fluorine Radioisotopes pharmacokinetics
Hepatic Encephalopathy drug therapy
Ibuprofen therapeutic use
Pyrazoles pharmacokinetics
Pyrimidines pharmacokinetics
Rats
Receptors, GABA-A analysis
Treatment Outcome
Fluorine Radioisotopes administration & dosage
Hepatic Encephalopathy diagnosis
Positron-Emission Tomography methods
Pyrazoles administration & dosage
Pyrimidines administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1838-7640
- Volume :
- 6
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Theranostics
- Publication Type :
- Academic Journal
- Accession number :
- 27279913
- Full Text :
- https://doi.org/10.7150/thno.15362