Preparation of ³H-23-hydroxylbetulinic acid and in vivo evaluations in mice

The purpose of this work is to study the preparation and pharmacokinetics in mice of tritium-labeled 23-hydroxylbetulinic acid (³H-23-HBA). ³H-23-HBA was synthesized by oxidation with manganese and deoxidization with tritium-labelled sodium borohydride. The purity and stability of ³H-23-HBA were evaluated by HPLC and TLC, and the dynamic distribution in ICR mice and liver cancer HepA tumor-bearing mice were studied. The results showed that the radiochemical purity was over 95% and the specific radioactivity was 3.33 × 10⁵Bq/μg (23-HBA); ³H-23-HBA in tetrahydrofuran was stable at -20°C; ³H-23-HBA cleared slowly in blood (MRT = 32.68 h) and about 60% of the total radioactivity in plasma was contributed by 23-HBA; and ³H-23-HBA was concentrated in gallbladder, liver and small intestine. In tumor-bearing mice, the uptakes of lung and gallbladder were higher than the normal mice, especially in the gallbladder. At 8 h post intravenous injection, the uptake of gallbladder was still as high as 106.89% ±47.4%ID/g organ. The tumor-to-muscle ratio was about 2. The purity of ³H-23-HBA is high and ³H-23-HBA is stable. So ³H-23-HBA appears to be fit for the pharmacokinetic study of 23-HBA.