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首页> 美国卫生研究院文献>Cancer Biology Therapy >A preclinical 188Re tumor therapeutic investigation using MORF/cMORF pretargeting and an antiTAG-72 antibody CC49
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A preclinical 188Re tumor therapeutic investigation using MORF/cMORF pretargeting and an antiTAG-72 antibody CC49

机译：使用MORF / cMORF预靶向和抗TAG-72抗体CC49的临床前188Re肿瘤治疗研究

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The utility of MORF/cMORF pretargeting for the radiotherapy of cancer requires further validation in tumored mice before clinical trials. We now report on a therapeutic study in mice pretargeted with MORF-CC49 (the anti-TAG-72 antibody CC49 conjugated with MORF, a phosphorodiamidate morpholino oligomer) and then targeted by 188Re-cMORF (a 188Re labeled complementary MORF). Before the dose-escalating therapeutic study, a pretargeting study in LS174T tumored mice was performed at tracer levels. By both necropsy and imaging, the tracer study showed that the whole body radioactivity was largely restricted to tumor in the mice pretargeted 48 h earlier with MORF-CC49 and the tumor radioactivity was retained over 90 h. After decay correction, a best-fit to the biodistribution provided the areas under the radioactivity curves (AUCs) used for the radiation dose estimates. The tumor to normal organ AUC ratios in all cases were greater than unity and ranged from 3 (kidneys) to 48 (muscle). Tumor growth was inhibited in the therapy study. At the highest 188Re dose of 1.40 mCi, a complete but temporary tumor remission was evident in three out of the five animals. Histological examination of tissues from these animals showed no evidence of cytotoxicity to normal tissues but obvious radiation damage to tumor. In conclusion, effective radiotherapy was achieved in a mouse model by MORF/cMORF pretargeting using 188Re as the therapeutic radionuclide and CC49 as the pretargeting antibody.
机译：在临床试验之前，MORF / cMORF预靶向工具在癌症放疗中的用途需要在肿瘤小鼠中进一步验证。现在，我们报道了一项针对小鼠的治疗研究，该小鼠预先靶向MORF-CC49（与MORF共轭的抗TAG-72抗体CC49，磷酸二酰胺基吗啉代寡聚物），然后被 188 Re-cMORF（a < sup> 188 重新标记为互补MORF）。在进行剂量递增治疗研究之前，以示踪剂水平对LS174T肿瘤小鼠进行了预靶向研究。通过尸检和影像学检查，示踪剂研究表明，在用MORF-CC49预先靶向的小鼠中，全身放射性很大程度上局限于肿瘤，并且在90 h内仍保留了肿瘤放射性。经过衰减校正后，对生物分布的最佳拟合提供了用于放射性剂量估算的放射性曲线（AUC）下的面积。在所有情况下，肿瘤与正常器官的AUC之比均大于1，范围为3（肾脏）至48（肌肉）。在治疗研究中肿瘤生长受到抑制。在最高 188 Re剂量为1.40 mCi时，五只动物中有三只显示出完全但暂时的肿瘤缓解。对这些动物组织的组织学检查没有发现对正常组织有细胞毒性的证据，但对肿瘤有明显的辐射损伤。总之，通过使用 188 Re作为治疗性放射性核素和CC49作为预靶向抗体的MORF / cMORF预靶向在小鼠模型中实现了有效的放射治疗。

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