Comparative study on the selectivity differences of 18F-TFQC and 18F-DPA-714 for TSPO gene polymorphisms and their PET imaging in rat neuroinflammation models
10.3760/cma.j.cn321828-20250319-00081
- VernacularTitle:18F－TFQC和 18F－DPA－714对TSPO基因多态性的选择性差异及在大鼠神经炎性反应模型中的PET显像对比
- Author:
Hongxing SU
1
;
Yufei MA
;
Qingyu LIN
;
Zhequan FU
;
Xinyan GAO
;
Pengcheng MA
;
Dai SHI
;
Zonghua LUO
;
Dengfeng CHENG
Author Information
1. 复旦大学附属中山医院核医学科，上海 200032
- Publication Type:Journal Article
- Keywords:
Neuroinflammatory diseases;
Receptors, GABA-A;
Pyrazoles;
Quinazolines;
Positron-emission tomography;
Rats;
18F-TFQC;
18F-DPA-714
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2025;45(8):458-463
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.
