~(32)P-磷酸铬-聚L-乳酸粒子植入实验鼠体内降解特性及代谢

目的 观察~(32)P-磷酸铬-聚L-乳酸(~(32)P-CP-PLLA)粒子植入实验鼠体内的降解特性及代谢.方法 KM小鼠72只,采用开腹或经皮穿刺法将~(32)P-CP-PLLA粒子分别植入小鼠肝、腹腔及腿部肌肉,粒子植入前活度为20.44～25.14 kBq,30 d内不同时间处死,取出粒子,取血及主要脏器测~(32)P放射性计数率,计算每克组织的百分剂量率(%ID/g),用扫描电镜动态观察粒子形态变化.SD大鼠5只,肝内植入粒子后代谢笼饲养,每24小时测量粪便及尿液放射性,计算~(32)P30 d排泄率.计量数据以-x±s表示,采用SPSS 13.0软件进行统计分析.结果 KM小鼠体内生物分布显示~(32)P-CP-PLLA 粒子植入后无一发生粒子移位,释出的~(32)PP在重要脏器和组织中放射性分布略高于本底水平.30 d内组织脏器计数率之和呈现阶段性变化:肝组1～5 d各脏器摄取总值极少,6～10 d略增多,11～20 d又趋减少,21～25 d摄取再次增多,达到峰值(622±11)计数/min,26-30 d略有下降;肌肉组变化与肝组相似,唯峰时提前(15 d),且峰值相对较低,为(403±14)计数/min;腹腔组重要脏器摄取呈持续低水平,无明显阶段性变化.粪便和尿液放射性峰值分别出现在第16天和第19天,排泄率分别为(0.82±0.20)%和(0.50±0.23)%,30 d总排泄率分别为4.08%和1.33%.结论 ~(32)P-CP-PLLA粒子作为一种新型治疗恶性肿瘤植入剂,在体内无脏器迁移,粒子呈现阶段性缓慢降解,降解物不具胶体特性,较少通过粪便和尿液排出体外,显示出良好的体内稳定性、靶向定位性和安全性.

Preliminary study on in vivo degradation and metabolism of ~(32)P-chromic phosphate-poly(L-lactic) acid seeds implanted into experimental mice

Objective Targeted positioning is one of the important characteristics of radionuclide brachytherapy.This study was to investigate the feasibility of preparation of ~(32)P-chromic phosphate(CP)with polymer materials poly(L-lactic)acid(PLLA)seed and to observe its in vivo degradation and metabolism in experimental mice.Methods ~(32)P-CP-PLLA seeds(with radioactivity of 20.44 kBq to 25.14 kBq)were im-planted into 72 KM mice through laparotomy or percutaneous puncture to the liver,abdominal cavity or limb muscles.The experimental mice were executed within 30 d at different time points.The seeds were taken out.~(32)P radioactive counting rate(min~(-1))in main organs was determined and the percentage of injection dosage in one gram tissue(%ID/g)was calculated.The morphological change of seeds was observed by scanning electron microscopy.The seeds were also implanted into the liver of five SD rats bred in metabolic cage.the radioactive counting rate(min~(-1))in 24 h feces and urine was determined and the ~(32)P30 d excre-tion rate was also caleulated.Results The biological distribution in KM mice revealed no displacement of seeds occurred.The released radioactivity of ~(32)P in main organs or tissues was slightly higher than that of background level.The culminated counting rate in organs or tissues within 30 d changed in different phases:the aggregated uptake in liver was very low during 1-5 d,slightly increased during6-10 d,decreased during 11-20 d and increased again during 21-25 d and reached its peak value(622±11)/min,then slightly de-creased during 26-30 d;the changes in muscle were similar to those in liver but the peak appeared earlier (15 d)with relatively lower value(403±14)/min.In abdominal cavity group,the uptake value in impor-tant organs maintained a persistent lower level with no prominent phase changes.The peak values in feces and urine appeared on 16 d and 19 d.the rates of excretion(30 d total excretion)were 4.08% and 1.33% respectivelv. Conclusions ~(32)P-CP-PLLA seeds,as newly prepared implants for the potential treat-merit of malignant tumor,have no displacement in organs of the animal,with very low radioactivity distributed in the body.Seeds presented phased slow degradation,no characteristics of colloids observed in the degraded yields,only trace amount of radioactivity excreted through feces and urine.~(32)P-CP-PLLA presented fairly stability and targeting orientation.