Preparation and imaging of 18 F-VUIIS1008 targeting TSPO in rheumatoid arthritis model
10.3760/cma.j.issn.2095-2848.2019.07.006
- VernacularTitle:靶向TSPO显像剂18F-VUIIS1008的制备及其对类风湿关节炎模型的显像
- Author:
Liangliang WANG
1
,
2
;
Zhenyu HOU
;
Xinhui SU
;
Huanhua WU
;
Qiang WANG
;
Wentao DONG
;
Li-Chun CHEN
;
Zhide GUO
;
Chao MA
;
Fu SU
Author Information
1. 厦门大学附属中山医院核医学科 361004
2. 临沂市人民医院核医学科 276000
- Keywords:
Membrane transport proteins;
Pyrazoles;
Pyrimidines;
Fluorine radioisotopes;
Arthritis;
rheumatoid;
Positron-emission tomography;
Tomography;
X-ray computed;
Mice
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2019;39(7):408-413
- CountryChina
- Language:Chinese
-
Abstract:
Objective To synthesize a novel 18 F labeled probe targeting translocator protein ( TSPO) ligand 2-( 5, 7-diethyl-2-( 4-( 2-fluoroethoxy ) phenyl ) pyrazolo [ 1, 5-a ] pyrimidin-3-yl )-N, N-diethylacet-amide (VUIIS1008), and evaluate its biodistribution and imaging in rheumatoid arthritis (RA) model. Methods The tosylate substrate was labeled with 18 F using a tosyloxy for fluorine nucleophilic aliphatic substitution to obtain 18 F-VUIIS1008. The labeling efficiency, radiochemical purity, and stability in vitro were determined. In vitro cellular uptake and competitive binding assay were performed on RAW264.7 mac-rophage cells. Biodistribution and microPET/CT imaging were investigated on RA mice established by Com-plete Freund's Adjuvant. Two-sample t test was used to analyze the data. Results 18 F-VUIIS1008 was syn-thesized with the labeling yield up to (41.00±5.00)％, the radiochemical purity>98.00％, and the specific radioactivity >1. 52 × 108 MBq/mmol. 18 F-VUIIS1008 was highly stable with the radiochemical purity >98. 00％ at 4 h after incubation in mouse serum. In vitro, it also exhibited high specific TSPO binding in RAW264.7 macrophage cells. The uptake ratio was (14.00±0.30)％ at 1 h after incubation, and decreased significantly ((4.00±0.70)％;t=12.894, P<0.05) after adding excessive unlabeled VUIIS1008. The half maximal inhibitory concentration (IC50) of 18F-VUIIS1008 binding to TSPO was 0.05 nmol/L in RAW264.7 macrophage cells. In vivo distribution results showed that the uptake of 18 F-VUIIS1008 in the left arthritic ankles reached the peak value of (1.33±0.02) percentage activity of injection dose per gram of tissue (％ID/g) at 1 h after injection. The radioactivity ratio of left ankle arthritic tissue to blood ( A/B) and to normal muscle ( A/M) was 4.40±0.22 and 1.65±0.07 respectively. MicroPET/CT imaging demonstrated that 18F-VUIIS1008 could specifically target and retained in the inflammation site. Conclusion 18 F-VUIIS1008 can be easily synthe-sized with high radiochemical purity and can clearly visualized in RA imaging with low background, suggesting its potential as a novel promising molecular probe targeting TSPO for RA PET imaging.
