氚标记23-羟基白桦酸的制备及其在动物体内的评价

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

制备氚标23-羟基白桦酸(3H-23-HBA),并对其在正常鼠及荷瘤鼠的体内分布进行初步探索。23-HBA经23位氧化、硼氚化钠还原后制得3H-23-HBA,考察了标记物的纯度和稳定性,并在ICR小鼠、接种肝癌HepA肿瘤的小鼠体内研究其生物分布特征。结果显示:(1)所得标记物放射化学纯度>95%,放射性比活度为3.33×105Bq/μg(23-HBA);(2)标记化合物的四氢呋喃溶液在–20℃稳定;(3)小鼠尾静脉注射3H-23-HBA(10mg/kg,3.7×105Bq/只)后,在血中清除慢,血浆中原形药约占60%;(4)小鼠尾静脉注射3H-23-HBA(10mg/kg,3.7×105Bq/只)后,在胆、肝、肠浓聚,消除慢;肿瘤鼠肺、胆中摄取高于正常鼠,尤其是胆,至注射后8h仍高达106.89%±47.4%ID/g。实体瘤与对侧肌肉组织的摄取比约为2。3H-23-HBA纯度高,稳定性好,适用于23-HBA药代动力学研究。

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-beating mice were studied. The results showed that the radiochemical purity was over 95% and the specific radioactivity was 3.33×10^5Bq/μg （23-HBA）; ^3H-23-HBA in tetrahydrofuran was stable at -20℃; ^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.