摘要
目的验证^(99)Tc^m 直接法标记的重组入膜联蛋白 V(^(99)Tc^m-rh-Annexin V)用于早期评价放化疗后肿瘤组织细胞凋亡状态的可行性。方法将小鼠肝癌细胞(Hca-F25)接种于实验小鼠右腋下,8 d 后当肿瘤生长至直径约1 cm 时,将模型鼠分为 A(化疗组,13只)、B(放疗组,10只)、C(荷瘤对照组,12只)3组。其中 A、C 组按注射示踪剂后不同时间(1、4、6 h)各分为3个亚组(A1组3只,A2组4只,A3组6只;C1组3只,C2组4只,C3组5只);A 组接受环磷酰胺单次化疗(按体重150 mg/kg,腹腔内注射),C 组腹腔内注射同等量生理盐水,20 h 后 A、C 组鼠尾静脉注射^(99)Tc^m-rh-Annexin V 3.7MBq(0.5 μg)/只。B 组按不同吸收剂量(2、5、10 Gy)分为3个亚组(B1组4只,B2组3只,B3组3只),放疗后1 h 注射与 A、C 组相同剂量示踪剂,6 h 后显像。小鼠模型显像后即刻处死,取组织(肿瘤、血、肌肉)称重后,测量放射性计数,并计算每克组织百分注射剂量率(%ID/g)及肿瘤(T)/肌肉(M)、T/血液(B)放射性比值,应用流式细胞仪检测细胞凋亡百分率。结果 A、B 组小鼠肿瘤组织中凋亡细胞百分率[(11.16±3.83)%、(17.40±5.20)%]均明显高于 C 组[(2.11±1.51)%,F=56.414、94.748,P<0.001];A2、A3及 B 组肿瘤组织%ID/g 均明显高于 C2及 C3组(F 值分别为14.307、7.074、28.672,P 均<0.05),且与凋亡细胞百分率呈明显正相关(A2、A3组:r=0.813,P=0.002;B组:r=0.780,P=0.004),而 C 组肿瘤组织%ID/g 与凋亡细胞百分率无相关性(r=-0.238,P=0.229)。结论接受放疗或化疗后,小鼠肝癌组织对^(99)Tc^m-rh-Annexin V 的摄取明显增加,且其摄取程度与肿瘤组织内凋亡细胞量呈明显正相关;应用^(99)Tc^m-rh-Annexin V 显像可较准确地反映治疗后早期肿瘤组织细胞凋亡的状态。
Objective To evaluate the efficacy of ^99Tc^m labeled recombinant hunkan Annexin V（^99Tc^m- rh-AnnexinV） in evaluating apoptosis after radio- or chemotherapy in Hca-F25 （hepatoma cell line） mice models. Methods The tumor models were established in mice at 8th day （tumor size around 1 cm in diameter） after treated with Hca-F25 （subcutaneous injection at right axillary）. Mice were divided into three groups, Group A （ n = 13） were chemotherapy, group B （ n = 10） were radiotherapy and group C （ n = 12 ） were for control. For groups A and C, the imaging time interval were 1 h （ n = 3 for group A and n = 3 for group C ）, 4 h （ n = 4 for group A and n = 4 for group C） and 6 h （ n = 6 for group A and n = 5 for group C） after intravenous injection （from tail vein） of ^99Tc^m-rh-Annexin V. For group B, ^99Tc^m-rh-Annexin V was given in all at 1 h af- ter radiation therapy （n =4 for 2 Gy, n=3 for 5 Gy and n =3 for 10 Gy）. At 6 h after injection, all had scintigraphic images, After completion of data acquisition, all mice were sacrificed to evaluate the biodistribution of ^99Tc^m-rh-Annexin V in each tissue and were expressed as the percentage activity of injection dose per gram of tissue （ % ID/g ）. The percentage of cell apoptosis was calculated with Annexin V/PI flow cytometry （Annexin V ^±/PI^- was positive）, Results Significantly higher cell apoptotic rates were observed in the treated mice than in the control mice [ （ 11. 16 ± 3, 83 ） % vs （ 2. 11 ± 1.51 ） % for chemotherapy group, F=56.414, P〈0.001; （17.40 ±5.20）% vs （2. 11 ±1,51）% for radiotherapy group,F= 94. 748, P 〈 0. 0011, Besides, positive correlations were observed between the percentage of cell apoptosis and the biodistribution of ^99Tc^m-rh-AnnexinV in tumor in chemotherapy treated （4 and 6 h, F = 14. 307, 7. 074, 28. 672, all P 〈 0.05, respectively） and radiotherapy treated mice and control with r = 0. 813 （ P = 0. 002 ） for chemotherapy treated 4 and 6 h mice and r =
出处
《中华核医学杂志》
CAS
CSCD
北大核心
2006年第5期268-272,共5页
Chinese Journal of Nuclear Medicine
