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86/90Y-Labeled Monoclonal Antibody Targeting Tissue Factor for Pancreatic Cancer Theranostics.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-03-23 , DOI: 10.1021/acs.molpharmaceut.0c00127 Carolina A Ferreira 1 , Emily B Ehlerding 2 , Zachary T Rosenkrans 3 , Dawei Jiang 2 , Tuanwei Sun 2 , Eduardo Aluicio-Sarduy 2 , Jonathan W Engle 2 , Dalong Ni 2 , Weibo Cai 1, 2, 3
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-03-23 , DOI: 10.1021/acs.molpharmaceut.0c00127 Carolina A Ferreira 1 , Emily B Ehlerding 2 , Zachary T Rosenkrans 3 , Dawei Jiang 2 , Tuanwei Sun 2 , Eduardo Aluicio-Sarduy 2 , Jonathan W Engle 2 , Dalong Ni 2 , Weibo Cai 1, 2, 3
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Pancreatic cancer is highly aggressive, with a median survival time of less than 6 months and a 5-year overall survival rate of around 7%. The poor prognosis of PaCa is largely due to its advanced stage at diagnosis and the lack of efficient therapeutic options. Thus, the development of an efficient, multifunctional PaCa theranostic system is urgently needed. Overexpression of tissue factor (TF) has been associated with increased tumor growth, angiogenesis, and metastasis in many malignancies, including pancreatic cancer. Herein, we propose the use of a TF-targeted monoclonal antibody (ALT836) conjugated with the pair 86/90Y as a theranostic agent against pancreatic cancer. For methods, serial PET imaging with 86Y-DTPA-ALT836 was conducted to map the biodistribution the tracer in BXPC-3 tumor-bearing mice. 90Y-DTPA-ALT836 was employed as a therapeutic agent that also allowed tumor burden monitoring through Cherenkov luminescence imaging. The results were that the uptake of 86Y-DTPA-ALT836 in BXPC-3 xenograft tumors was high and increased over time up to 48 h postinjection (p.i.), corroborated through ex vivo biodistribution studies and further confirmed by Cherenkov luminescence Imaging. In therapeutic studies, 90Y-DTPA-ALT836 was found to slow tumor growth relative to the control groups and had significantly smaller (p < 0.05) tumor volumes 1 day p.i. Histological analysis of ex vivo tissues revealed significant damage to the treated tumors. The conclusion is that the use of the 86/90Y theranostic pair allows PET imaging with excellent tumor-to-background contrast and treatment of TF-expressing pancreatic tumors with promising therapeutic outcomes.
中文翻译：
用于胰腺癌治疗的86 / 90Y标签的单克隆抗体靶向组织因子。
胰腺癌具有高度侵袭性，中位生存时间少于6个月，五年总生存率约为7％。PaCa预后不良主要是由于其诊断的晚期阶段和缺乏有效的治疗选择。因此，迫切需要开发高效，多功能的PaCa治疗体系。组织因子（TF）的过表达与包括胰腺癌在内的许多恶性肿瘤的肿瘤生长，血管生成和转移增加有关。在本文中，我们建议使用与86 / 90Y对偶联的TF靶向单克隆抗体（ALT836）作为抗胰腺癌的治疗治疗剂。对于方法，使用86Y-DTPA-ALT836进行连续PET成像以绘制示踪剂在BXPC-3荷瘤小鼠中的生物分布。90Y-DTPA-ALT836被用作治疗剂，还允许通过Cherenkov发光成像监测肿瘤负荷。结果是，BXPC-3异种移植肿瘤中的86Y-DTPA-ALT836吸收率很高，并且在注射后第48小时（pi）随时间增加，这通过离体生物分布研究得到了证实，并被Cherenkov发光成像进一步证实。在治疗研究中，发现90Y-DTPA-ALT836相对于对照组减慢了肿瘤的生长，并且在pi 1天时肿瘤体积明显更小（p <0.05），离体组织的组织学分析显示对治疗的肿瘤有明显的损害。
更新日期：2020-03-23
中文翻译：
用于胰腺癌治疗的86 / 90Y标签的单克隆抗体靶向组织因子。
胰腺癌具有高度侵袭性，中位生存时间少于6个月，五年总生存率约为7％。PaCa预后不良主要是由于其诊断的晚期阶段和缺乏有效的治疗选择。因此，迫切需要开发高效，多功能的PaCa治疗体系。组织因子（TF）的过表达与包括胰腺癌在内的许多恶性肿瘤的肿瘤生长，血管生成和转移增加有关。在本文中，我们建议使用与86 / 90Y对偶联的TF靶向单克隆抗体（ALT836）作为抗胰腺癌的治疗治疗剂。对于方法，使用86Y-DTPA-ALT836进行连续PET成像以绘制示踪剂在BXPC-3荷瘤小鼠中的生物分布。90Y-DTPA-ALT836被用作治疗剂，还允许通过Cherenkov发光成像监测肿瘤负荷。结果是，BXPC-3异种移植肿瘤中的86Y-DTPA-ALT836吸收率很高，并且在注射后第48小时（pi）随时间增加，这通过离体生物分布研究得到了证实，并被Cherenkov发光成像进一步证实。在治疗研究中，发现90Y-DTPA-ALT836相对于对照组减慢了肿瘤的生长，并且在pi 1天时肿瘤体积明显更小（p <0.05），离体组织的组织学分析显示对治疗的肿瘤有明显的损害。
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