Garnuszek Piotr
Department of Radiopharmaceuticals, The National Institute of Public Health, Warsaw, Poland.
Nucl Med Rev Cent East Eur. 2004;7(2):113-6.
Recently, a new PtCl2-histamine complex, and its radioactive analogues labelled with I-131 and I-125 have been synthesised and investigated both in vitro and in vivo. In this preliminary report the survival rate of radioactive platinum-[125I] histamine therapy in tumour-bearing mice is demonstrated.
A murine model of transplantable colon adenocarcinoma (C38) in C57BL/6 mice (15 days postimplantation) was used for the experiment. Three groups of animals were treated every 2-3 days with five intraperitoneal injections of the following preparations: PtCl2Hist (total dose of Pt--125 micromol/kg), PtCl2[125I]Hist (total dose of I-125--4.2 MBq; Pt--13 micromol/kg), and "Active/Cold"--PtCl2[125I]Hist/PtCl2Hist (I-125--4.2 MBq; Pt--125 micromol/kg). A solution of 15% dimethylformamide in saline was applied to the control group. A survival analysis with the Kaplan-Meier estimation of survival curves and a statistical comparison by a log-rank test was applied to evaluate the anticancer activity of the tested preparations.
Treatment of the animals with platinum-histamine preparations resulted in a significant prolongation of survivals, especially if the radioactive complex with carrier-added PtCl2Hist (p < 0.005) was applied. The highest, almost a 60% prolongation of survival was observed in the Active/Cold group (MStr/MScon ratio = 1.58, 95% CI 1.22-1.93). For this group there was the lowest risk of death (hazard ratio HR = 0.29), whereas HR = 0.45 and 0.47 were found in the animals treated with unattended PtCl2Hist and 125I-labelled complex, respectively.
The significant enhancement of in vivo anti-cancer activity by a concomitant combination of the therapeutic factors, i.e. cytotoxic/cytostatic activity of the platinum(II)-histamine and the Auger electrons effects generated by the attached I-125 radionuclide, was found on the murine model of transplantable colon adenocarcinoma.
最近，一种新的PtCl₂ - 组胺络合物及其用I - 131和I - 125标记的放射性类似物已被合成，并在体外和体内进行了研究。在这份初步报告中，展示了放射性铂 - [¹²⁵I]组胺疗法在荷瘤小鼠中的存活率。
使用C57BL/6小鼠（植入后15天）的可移植结肠腺癌（C38）小鼠模型进行实验。三组动物每2 - 3天接受五次腹腔注射以下制剂：PtCl₂Hist（铂的总剂量 - 125微摩尔/千克）、PtCl₂[¹²⁵I]Hist（I - 125的总剂量 - 4.2兆贝可；铂 - 13微摩尔/千克），以及“活性/冷” - PtCl₂[¹²⁵I]Hist/PtCl₂Hist（I - 125 - 4.2兆贝可；铂 - 125微摩尔/千克）。对照组给予15%二甲基甲酰胺的生理盐水溶液。应用Kaplan - Meier生存曲线估计进行生存分析，并通过对数秩检验进行统计比较，以评估受试制剂的抗癌活性。
用铂 - 组胺制剂治疗动物可显著延长生存期，特别是应用添加载体的PtCl₂Hist放射性络合物时（p < 0.005）。在“活性/冷”组中观察到生存期延长最高，几乎延长了60%（MStr/MScon比值 = 1.58，95%置信区间1.22 - 1.93）。该组的死亡风险最低（风险比HR = 0.29），而在分别接受未添加载体的PtCl₂Hist和¹²⁵I标记络合物治疗的动物中，HR分别为0.45和0.47。
在可移植结肠腺癌小鼠模型中发现，通过治疗因素的联合组合，即铂（II） - 组胺的细胞毒性/细胞生长抑制活性以及附着的I - 125放射性核素产生的俄歇电子效应，可显著增强体内抗癌活性。
