Preparation of 18 F-DPA-714 and its biodistribution in rodents
10.3760/cma.j.issn.2095-2848.2017.10.007
- VernacularTitle:18 F-DPA-714的制备及其在动物体内的生物学分布
- Author:
Wei HU
1
;
Jun ZHAO
;
Min YANG
;
Yihui GUAN
;
Chuantao ZUO
;
Fengchun HUA
;
Donghui PAN
Author Information
1. 复旦大学附属华山医院PET中心
- Keywords:
DPA-714;
Isotope labeling;
Fluorine radioisotopes;
Positron-emission tomography;
Mice;
Rats
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2017;37(10):632-636
- CountryChina
- Language:Chinese
-
Abstract:
Objective To synthesize 18 F-DPA-714 and to study its labeling rate, radiochemical purity, stability and biological characteristics. Methods 18F-was reacted with K2CO3/K2.2.2 and then en-gaged in nucleophilic substitution with DPA-714. The crude product was purified by aluminum column and semi-preparation HPLC. The stability of 18 F-DPA-714 was identified in PBS and plasma. The lipid-water partition coefficient (LogP) was determined. Biodistribution analysis and microPET imaging were performed on mice and rats respectively. Results It took about 25 min for synthesizing 18 F-DPA-714, the radiochemi-cal yield was 31.6% (decay not corrected), and the radiochemical purity was ≥99%. The product re-mained stable within 4 h. The LogP of 18 F-DPA-714 was 2.71. Pharmacokinetics of 18 F-DPA-714 was more in line with the two compartment model, with the distribution half-life ( T1/2α) of 2.40 min and the elimina-tion half-life( T1/2β) of 69.15 min. 18 F-DPA-714 was quickly uptaken by tissues after the tail vein injection. It mainly distributed in the lungs, kidneys, and heart, with the radioactive uptake values of (17.85±7.52)%ID/g, (15.41±1.80) %ID/g and (10.56±0.94) %ID/g at 30 min post-injection, respectively. 18F-DPA-714 was mainly metabolized through the liver, and excreted by the kidneys. The uptake in bones was stable. PET dynamic scanning showed that 18 F-DPA-714 accumulated in the brain of aged rats and cleared slowly within 60 min. Conclusions 18 F-DPA-714 prepared in this study has high labeling rate, short synthesis time and small precursor dosage. It displays good biological distribution and blood-brain barrier permeability characteristics.
