一种碘代二肽胺的体内外评价

In vitro and in vivo evaluation of p-Boc-Trp-Trp-NH(CH_2)_6NH-PO(ONH_4)-O-Ph^(131)I

为了探索前期自行合成的一种碘(131I)代二肽胺作为放射性药物的可能性,本文对其体外稳定性、亲脂性、急性毒性进行了考察。首先采用封管法对二肽胺进行了碘的标记,获得了标记率为85%左右的配合物;通过将配合物放置不同时间测量络合率的变化得到配合物的稳定性结果;采用摇瓶法来考察配合物的亲脂性;对配合物对实验动物的肝脏功能、外周血象的影响作了考察。结果说明,配合物是亲脂性的,毒性较低,3d后的脱碘率为13%左右。成功建立了VX2肝癌单发肿瘤兔模型,得到了配合物在正常小鼠和肿瘤大白兔体内的分布结果,配合物在动物模型以及在正常小鼠的体内分布趋势比较一致,配合物比较倾向于浓集于脂肪组织,在肿瘤组织中的滞留量相对较高,表现出作为肿瘤治疗药物的潜在可能性,但清除较快,可以作进一步的研究,提高标记物的体内稳定性,以延长配合物在靶向组织中的浓集时间。

Stability in vitro, lipophility and acute toxicity of p-Boc-Trp-Trp-NH（CH2）6NH-PO （ONH4）-O-Ph^131I are studied in this work. The complex, with labeling yield of around 85%, was obtained using sealed-tube method. Stability of the complex was obtained by measuring labeling yield at different time. Its lipophility was studied through swaging-flask method, and its impacts to liver function and peripheral blood of the experimental animals were also studied. The results indicate the complex is lipophilic and less toxic, and the iodine removal rate was about 13% three days later. The rabbit model with VX2 liver tumor was established successfully. The organ and tissue uptake and retention of p-Boc-Trp-Trp-NH（CH2）6NH- PO（ONH4）-O-Ph^131I were studied in a model subject. Blood, liver, lungs, kidneys, spleen and tumour tissue samples were assayed in a well counter for radioactivity and the results were compared with the biodistribution studies in five normal mice. The complex trends to concentrate into adipose tissues in tumour-bearing and normal animals, and the uptake rate in tumor tissue is relatively high, hence its potential possibility as radiopharmaceuticals. But it cleared quickly. Further researches are underway to improve the stability of complexes to prolong concentration time in target tissue.