Synthesis of a18F-labeled Berberine derivative and the in vitro and in vivo evaluation as a PET tracer probably targeting α-adrenergic receptor

1397 Introduction: Berberine (BBR), a natural alkaloid isolated from the Coptis Chinensis, is believed to be effective in regulation of gut microbiome and treatment of cardiovascular diseases. It showed antiarrhythmic effect by blocking α-adrenergic receptor. However, the mechanism is still inconclusive. This study aims to synthesize and evaluate a new Berberine derivative (18F-BBRD), as a potential molecular imaging agent to investigate the mechanisms of BBR and probably targeting α-adrenergic receptor. Methods: A berberine derivative (BBRD) precursor was prepared and labeled with 18F. The in vitro analysis included stability, plasma protein binding rate, lipid-water partition coefficient, etc. Groups of mice were used for in vivo pharmacokinetics and biodistribution studies and rats for microPET imaging after both intragastric administration and intravenous injection. Results: Thesynthesis lasted for nearly 1 h. The yield was >5.0% without decay correction and the radiochemical purity was >95%. 18F-BBRD showed high stability in 0.9% NaCl and plasma within 4 hours. Plasma protein binding rate of 18F-BBRD was 9.7%. The lipid-water partition coefficient (log P) for 18F-BBRD was 0.84. Up to 6 h, the intragastric administrated 18F-BBRD was rarely absorbed. After the tail vein injection, 18F-BBRD was mainly distributed in the kidneys, heart, liver, and bowel. The cardiac uptake reached a peak at 30 min and remained a plateau up to 4 h, whereas the uptake in the kidneys and liver decreased rapidly.Conclusion: A Berberine derivative, 18F-BBRD, was successfully synthesized and labeled with 18F. The in vitro and in vivo analysis showed high stability, proper solubility, and suitable biodistribution of the tracer for molecular imaging, probably in evaluation of cardiovascular diseases.