Radionuclide therapy of bevacizumab-based PNA-mediated pretargeting.

IF 1.3 4区 医学 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Nuclear Medicine Communications Pub Date : 2024-11-01 Epub Date: 2024-07-16 DOI:10.1097/MNM.0000000000001877
JingXuan Yan, Peng Zhao, Yuanyuan Li, Jing Wang, Xia Yang, Hongbo Li, Liangang Zhuo, Wei Liao, Wenqi Fan, Yaodan Jia, Hongyuan Wei, Yue Chen
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Abstract

Background: The radionuclide-labeled bevacizumab (BV) is a potential therapeutic approach for vascular endothelial growth factor overexpressed tumors. Because of its large molecular weight, BV is cleared slowly in vivo , which caused damage to healthy tissues and organs. On account of this situation, using the pretargeting strategy with DNA/RNA analogs, such as peptide nucleic acid (PNA), is an effective way of treating solid tumors.

Methods: The BV-PNA conjugate (BV-PNA-1) was injected intravenously as the pretargeted probe, which was specifically accumulated in a solid tumor and gradually metabolically cleared. Then the [ 177 Lu]Lu-labeled complementary PNA strand ([ 177 Lu]Lu-PNA-2) as the second probe was injected, and bound with BV-PNA-1 by the base complementary pairing. In this study, the BV-based PNA-mediated pretargeting strategy was systematically studied, including stability of probes, specific binding ability, biodistribution in animal model, evaluation of single photon emission computed tomography/computed tomography imaging, and therapeutic effect.

Results: Compared with group A ([ 177 Lu]Lu-BV), the group B (BV-PNA-1 + [ 177 Lu]Lu-PNA-2) showed lower blood radiotoxicity (22.55 ±1.62 vs. 5.18 ± 0.40%, %ID/g, P  < 0.05), and similar accumulation of radioactivity in tumor (5.32 ± 0.66 vs. 6.68 ± 0.79%, %ID/g, P  > 0.05). Correspondingly, there was no significant difference in therapeutic effect between groups A and B.

Conclusion: The PNA-mediated pretargeting strategy could increase the tumor-to-blood ratio, thereby reducing the damage to normal tissues, while having a similar therapeutic effect to solid tumor. All the experiments in this study showed the potential and effectiveness of pretargeting radioimmunotherapy.

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基于 PNA 介导的贝伐珠单抗前靶向的放射性核素疗法。
背景:放射性核素标记的贝伐珠单抗(BV)是治疗血管内皮生长因子过度表达肿瘤的一种潜在方法。由于贝伐珠单抗分子量较大,在体内清除缓慢,对健康组织和器官造成损伤。鉴于这种情况,使用DNA/RNA类似物(如肽核酸(PNA))进行预靶向是治疗实体瘤的一种有效方法:方法:静脉注射BV-PNA共轭物(BV-PNA-1)作为预靶向探针,该探针在实体瘤中特异性蓄积并逐渐代谢清除。然后注射[177Lu]Lu 标记的互补 PNA 链([177Lu]Lu-PNA-2)作为第二探针,通过碱基互补配对与 BV-PNA-1 结合。本研究对基于 BV 的 PNA 介导的预靶向策略进行了系统研究,包括探针的稳定性、特异性结合能力、动物模型的生物分布、单光子发射计算机断层扫描/计算机断层扫描成像评估以及治疗效果:结果:与 A 组([177Lu]Lu-BV)相比,B 组(BV-PNA-1 + [177Lu]Lu-PNA-2)的血液放射性毒性较低(22.55 ±1.62 vs. 5.18 ± 0.40%,%ID/g,P 0.05)。相应地,A 组和 B 组的治疗效果没有明显差异:结论:PNA 介导的预靶向策略可以提高肿瘤与血液的比例,从而减少对正常组织的损伤,同时对实体瘤具有相似的治疗效果。本研究的所有实验都显示了放射免疫前靶向治疗的潜力和有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.20
自引率
6.70%
发文量
212
审稿时长
3-8 weeks
期刊介绍: Nuclear Medicine Communications, the official journal of the British Nuclear Medicine Society, is a rapid communications journal covering nuclear medicine and molecular imaging with radionuclides, and the basic supporting sciences. As well as clinical research and commentary, manuscripts describing research on preclinical and basic sciences (radiochemistry, radiopharmacy, radiobiology, radiopharmacology, medical physics, computing and engineering, and technical and nursing professions involved in delivering nuclear medicine services) are welcomed, as the journal is intended to be of interest internationally to all members of the many medical and non-medical disciplines involved in nuclear medicine. In addition to papers reporting original studies, frankly written editorials and topical reviews are a regular feature of the journal.
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