{"title":"Radionuclide therapy of bevacizumab-based PNA-mediated pretargeting.","authors":"JingXuan Yan, Peng Zhao, Yuanyuan Li, Jing Wang, Xia Yang, Hongbo Li, Liangang Zhuo, Wei Liao, Wenqi Fan, Yaodan Jia, Hongyuan Wei, Yue Chen","doi":"10.1097/MNM.0000000000001877","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19708,"journal":{"name":"Nuclear Medicine Communications","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nuclear Medicine Communications","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MNM.0000000000001877","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0
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.
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.