ORIGINAL RESEARCH article
Front. Med.
Sec. Nuclear Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1507596
This article is part of the Research TopicWomen in Science - Nuclear Medicine 2024View all 4 articles
Affibody-based targeting agent 131 I-YZ HER2:V2 for HER2-positive ovarian cancer xenografts
Provisionally accepted
- Affiliated Hospital of Zunyi Medical University, Zunyi, China
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Background: The human epidermal growth factor receptor 2 (HER2) affibodies are multifunctional tools that, when labeled with radioactive isotopes, hold significant potential for the diagnosis and treatment of tumors exhibiting HER2 overexpression. This research focuses on the development of 131 I-labeled HER2 affibodies as targeted radionuclide therapy agents (TRNT) for HER2-positive Ovarian carcinoma.The YZ HER2:V2 affibody targeting HER2 was synthesized through genetic recombination.It was labeled with 131 I by the chloramine T method, and its radiochemical purity and stability were evaluated in vitro. The normal mice were subjected to a study on the pharmacokinetic characteristics of 131 I-YZ HER2:V2 . An assessment was conducted on the uptake in tumors, biological distribution, and potential for therapeutic use of 131 I-YZ HER2:V2 using a HER2-positive SKOV-3 nude mouse model. The HER2-negative ID-8 mouse model was used as a negative control.: 131 I-YZ HER2:V2 was easily prepared, and the nondecayed corrected yield of 131 I-YZ HER2:V2 affibody molecular probe was 96.06% ± 1.26%, showing good stability within 6h in both normal saline (NS) and fetal bovine serum (FBS). The affinity of 131 I-YZ HER2:V2 was 32.9 nmol/L by cell binding assay. Scintigraphy revealed rapid uptake of the tracer in HER2-positive tumors. The retention of radioactive metabolites in the stomach, kidney, and bladder indicates that radioactive metabolites are mainly excreted through the gastrointestinal tract and urinary system. No substantial radioactive accumulation was observed in the heart, liver, lungs, or muscle tissue. Notably, significant renal retention was also evident based on in vitro biological distribution analysis. Tumor accumulation, extended retention, and advantageous distribution were observed in mice with HER2-positive tumors. Mice treated with 131 I-YZ HER2:V2 showed reduced tumor growth and prolonged survival. In the negative control group, there was no obvious aggregation and inhibition of tumors, and radioactive uptake in the kidney and gastrointestinal tract was also observed. Conclusion : 131 I-YZ HER2:V2 has the potential to be explored as a new method for TRNT in HER2-positive ovarian cancer.
Keywords: Human epidermal growth factor receptor 2, Affibody, 131 I, Radionuclide targeted therapy, HER2
Received: 08 Oct 2024; Accepted: 19 Jun 2025.
Copyright: © 2025 Hu, Hu, Li, Wang and Cai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jiong Cai, Affiliated Hospital of Zunyi Medical University, Zunyi, China
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