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

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: The synthesis 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.

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