~(32)P-磷酸铬-聚L-乳酸缓释粒子近距离治疗裸鼠前列腺癌的实验研究

目的:探讨32P-磷酸铬-聚L-乳酸(32P-CP-PLLA)缓释粒子局部植入对裸鼠前列腺癌的治疗作用。方法:建立裸鼠前列腺癌皮下移植瘤模型,然后将裸鼠进行如下分组,A、B、C为高、中、低剂量(14.8、7.4、3.7MBq)32P-CP-PLLA缓释粒子组,D、E、F为同等活度125I粒子组(14.8、7.4、3.7MBq),G为空白对照组,每组6只,植入粒子后观察:①32P缓释粒子和125I粒子对瘤体的病理形态学以及抑瘤率的影响;②外周血计数白细胞(WBC)和血小板(PLT)变化,观察血液毒性反应。结果:治疗21d后处死裸鼠,病理形态学显示实体瘤组织呈出血、坏死性改变,抑瘤率与给药剂量呈正相关,给药剂量为3.7、7.4、14.8MBq时,21d时各组抑瘤率[(65.72±6.95)%、(77.58±4.32)%、(82.64±4.03)%]、白细胞计数[(1.72±0.37)×109/L、(1.23±0.27)×109/L、(0.86±0.25)×109/L]、血小板计数[(1.18±0.11)×1011/L、(0.97±0.10)×1011/L、(0.72±0.11)×1011/L]、体重[(18.60±0.66)g、(17.60±0.39)g、(16.90±0.68)g]与相应各剂量的125I粒子组(3.7、7.4、14.8MBq)的抑瘤率[(35.61±5.61)%、(43.30±6.94)%、(69.01±4.98)%]、以及125I粒子组和空白对照组的白细胞计数[(1.45±0.40)×109/L、(0.51±0.24)×109/L、(0.37±0.26)×109/L、(3.96±0.26)×109/L]、血小板计数[(0.97±0.15)×1011/L、(0.76±0.16)×1011/L、(0.64±0.12)×1011/L、(2.89±0.21)×1011/L]、体重[(17.86±0.60)g、(15.56±0.39)g、(14.61±0.65)g、(19.95±0.73)g]比较差异有统计学意义(P均<0.01)。结论:32P-CP-PLLA缓释粒子瘤体植入治疗前列腺癌为一种安全、简便、有效的核素介入疗法。

Implantation brachytherapy with 32P-chromic phosphate-poly (L-lactide) delayed-release particles for prostate cancer in nude mice

Objective:To study the effects of implantation brachytherapy with delayed-release particles of 32P-chromic phosphate-poly (L-lactide) (32P-CP-PLLA) on prostate cancer (PCa) in nude mice. Methods:We established a subcutaneous transplantable PCa model in nude mice,and randomly divided them into six groups,Groups A,B and C implanted intratumorally with 32P-CP-PLLA delayed-release particles at 3.7,7.4 and 14.8 MBq,Groups D,E and F with 125I particles at the same doses as the former three,and another six nude mice were included in Group G as the blank control. Then we killed the mice at 21 days after the treatment,observed the effects of the particles on the morphology of the tumor and their inhibition of tumor growth,counted WBCs and platelets (PLTs) in the peripheral blood,and detected the toxic reaction of the blood. Results:At 21 days after the treatment,the solid tumor tissues exhibited bleeding and necrotic changes,and the rates of tumor inhibition were positively correlated with the doses of administration. Groups A,B and C showed statistically significant differences from Groups D,E,F and G in the rate of tumor inhibition ([65.72±6.95]%,[77.58±4.32]% and [82.64±4.03]% versus [35.61±5.61]%,[43.30±6.94]% and [69.01±4.98]%),WBC count ([1.72±0.37]×109/L,[1.23±0.27]×109/L and [0.86±0.25]×109/L versus [1.45±0.40]×109/L,[0.51±0.24]×109/L,[0.37±0.26]×109/L and [3.96±0.26]×109/L),PLT count ([1.18±0.11]×1011/L,[0.97±0.10]×1011/L and [0.72±0.11]×1011/L versus [0.97±0.15]×1011/L,[0.76±0.16]×1011/L,[0.64±0.12]×1011/L and [2.89±0.21]×1011/L) and body weight ([18.60±0.66] g,[17.60±0.39] g and [16.90±0.68] g versus [17.86±0.60] g,[15.56±0.39] g,[14.61±0.65] g and [19.95±0.73] g) (P < 0.01). Conclusion:Intratumoral implantation of 32P-CP-PLLA is a safe,simple and effective radionuclide interventional therapy for prostate cancer.