Preparation of 18F-DPA-714 and its biodistribution in rodents

Objective To synthesize 18F-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 engaged in nucleophilic substitution with DPA-714. The crude product was purified by aluminum column and semi-preparation HPLC. The stability of 18F-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 18F-DPA-714, the radiochemical yield was 31.6% (decay not corrected), and the radiochemical purity was ≥99%. The product remained stable within 4 h. The LogP of 18F-DPA-714 was 2.71. Pharmacokinetics of 18F-DPA-714 was more in line with the two compartment model, with the distribution half-life (T1/2α) of 2.40 min and the elimination half-life(T1/2β) of 69.15 min. 18F-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 18F-DPA-714 accumulated in the brain of aged rats and cleared slowly within 60 min. Conclusions 18F-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. Key words: DPA-714; Isotope labeling; Fluorine radioisotopes; Positron-emission tomography; Mice; Rats