Radionuclide therapy of bevacizumab-based PNA-mediated pretargeting.

Autor:	Yan J; Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, .; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, ., Zhao P; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, .; National Health Commission Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), National Health Commission of the People's Republic of China and .; Key Laboratory of Nuclear Medicine and Molecular Imaging of Sichuan Province, People's Government of Sichuan Province, Mianyang, China., Li Y; Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, .; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, ., Wang J; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, .; National Health Commission Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), National Health Commission of the People's Republic of China and .; Key Laboratory of Nuclear Medicine and Molecular Imaging of Sichuan Province, People's Government of Sichuan Province, Mianyang, China., Yang X; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, .; National Health Commission Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), National Health Commission of the People's Republic of China and .; Key Laboratory of Nuclear Medicine and Molecular Imaging of Sichuan Province, People's Government of Sichuan Province, Mianyang, China., Li H; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, ., Zhuo L; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, .; National Health Commission Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), National Health Commission of the People's Republic of China and .; Key Laboratory of Nuclear Medicine and Molecular Imaging of Sichuan Province, People's Government of Sichuan Province, Mianyang, China., Liao W; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, .; National Health Commission Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), National Health Commission of the People's Republic of China and .; Key Laboratory of Nuclear Medicine and Molecular Imaging of Sichuan Province, People's Government of Sichuan Province, Mianyang, China., Fan W; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, ., Jia Y; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, ., Wei H; Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, .; Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, ., Chen Y; Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, .; Key Laboratory of Nuclear Medicine and Molecular Imaging of Sichuan Province, People's Government of Sichuan Province, Mianyang, China.
Jazyk:	angličtina
Zdroj:	Nuclear medicine communications [Nucl Med Commun] 2024 Nov 01; Vol. 45 (11), pp. 901-909. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1097/MNM.0000000000001877
Abstrakt:	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. (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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