Objective To sythesize 99Tcm labeled asparagine-glycine-arginine (NGR)- interferon (INF)-α2a and investigate its biodistribution by scintigraphy in tumor bearing mice. Methods NGR-INFα2a was labeled with 99Tcm by a two-step method. Ethylenedicysteine (EC) and MDP were used as bifunctional and transferring chelating agents. The bioactivities of 99Tcm-NGR-IFN-EC-NGR-IFN-α2a, EC-NGRIFN-α2a and NGR-IFN-α2a were compared using least significant difference t-test. The hepatoma bearing mice models were established by subcutaneous injection of MHCC97-H cells. The mice were randomly divided into eight groups and 7.4 MBq 99Tcm-NGR-IFN-α2a was injected via the tail vein. The tissue uptake of the radiolabeled compound was measured as % ID/g. The scintigraphy was performed at 0.5, 1, 2, 4,6, 8, 12 and 24 h after injection. ROI were drawn around tumor and non-tumor tissue and the radioactivity ratio of T/NT was calculated. Results Both the labeling efficiency and radiochemical purity of 99Tcm-EC-NGR-IFN-α2a were more than 90%. The radiochemical purity was 71% after 24 h in saline. The bioactivity showed no significant difference among three compounds (t = 0.416, 0. 120 and 1. 300, all P >0.05). The tracer was mainly excreted through alimentary and urinary tract within 24 h after injection. The peak values of % ID/g in kidney, liver, interstinal tract and tumor were 41.5 ± 8.0_ (at 8 h), 31.3 ± 5.0(at 6 h), 36.0 ± 7.8 (at 6 h), 43.0 ± 4.8 (at 4 h), respectively. The tracer was cleared quickly from the blood and the highest T/NT ratio was 16.5. The optimal imaging time ranged from 4 to 8 h after injection. Conclusions The sythesis of 99Tcm-NGR-IFN-α2a is applicable and it may be used as a potential tumor imaging agent.%目的 制备99Tcm标记天冬酰胺-甘氨酸-精氨酸(NGR)-干扰素-α2a(NGR-IFN-α2a),并研究其在荷瘤小鼠体内的动态分布及显像.方法 (1)双半胱氨酸(EC)作为双功能螯合剂合成EC-NGR-IFN-α2a,用MDP作为转移螯合剂,采用二步法对EC-NGR-IFN-α2a进行99Tcm标记,制备99Tcm-NGR-IFN-α2a,同时进行生物学活性测定,采用最小显著差异法t检验比较99Tcm-NGR-IFN-α2a与EC-NGR-IFN-α2a,NGR-IFN-α2a的生物活性;(2)建立肝癌MHCC97-H细胞严重联合免疫缺陷病(SCID)小鼠皮下移植瘤模型,采用随机数字表法分组,尾静脉注射99Tcm-NGR-IFN-α2a 7.4 MBq,分别于注射后0.5,1,2,4,6,8,12和24 h处死小鼠.取血、肝、肾、心、脾、肺、胃、肠、骨骼、肌肉及肿瘤组织,测质量及测放射性计数,经物理衰变校正后计算%ID/g,以肿瘤组织为靶组织,以肌肉组织为非靶组织,计算不同时间点T/NT放射性比值;(3)荷瘤小鼠经尾静脉注射7.4 MBq99TcmNGR-IFN-α2a,分别于注射后0.5,1,2,4,6,8,12和24 h行静态平面及SPECT/CT显像,采用ROI技术,同上计算不同时间点的T/NT比值.结果 99Tcm-NGR-IFN-α2a的标记率及放化纯均>90%,99Tcm-NGR-IFN-α2a在生理盐水中放置24 h后放化纯为71%;标记后生物学活性未发生改变(t=0.416,0.120和1.300,P均>0.05);99Tcm-NGR-IFN-α2a经小鼠尾静脉注射后24 h内,由泌尿和消化系统排泄,肾、肝、脾、肠道肿瘤的%ID/g值达到高峰的时间分别为8 h,6 h,6 h,4 h,高峰值分别为41.5±8.0,31.3±5.0,36.0±7.8,43.0±4.8;其在血液内清除迅速,其他组织器官的放射性随时间延长逐渐降低,T/NT比值最高可达16.5,最佳显像时间为注射后4～8 h.结论 99Tcm-NGR-IFN-α2a易于制备,具有良好的靶向性和显像效果.放射性核素标记的NGR-IFN-α2a有望成为一种新的肿瘤血管靶向性诊断与治疗药物.
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