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Published on: June 13, 2014
Affibody-based targeting agent 131I-YZHER2: V2 for HER2-positive ovarian cancer xenografts
Hongyu Hu1, Xianwen Hu1, Fangming Li1
1Department of Nuclear Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
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 131I-labeled HER2 affibodies as targeted radionuclide therapy agents (TRNT) for HER2-positive Ovarian carcinoma.
Methods:
The YZHER2: V2 affibody targeting HER2 was synthesized through genetic recombination. It was labeled with 131I 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 131I-YZHER2: V2. An assessment was conducted on the uptake in tumors, biological distribution, and potential for therapeutic use of 131I-YZHER2: V2 using a HER2-positive SKOV-3 nude mouse model. The HER2-negative ID-8 mouse model was used as a negative control.
Results:
131I-YZHER2: V2 was easily prepared, and the non-decayed corrected yield of 131I-YZHER2: V2 affibody molecular probe was 96.06% ± 1.26%, showing good stability within 6 h in both normal saline (NS) and fetal bovine serum (FBS). The affinity of 131I-YZHER2: 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 131I-YZHER2: 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:
131I-YZHER2: V2 has the potential to be explored as a new method for TRNT in HER2-positive ovarian cancer.
Insights
Iodine-131 labeled HER2 affibodies show promise for targeted radionuclide therapy in HER2-positive ovarian cancer. This study demonstrates their potential for tumor uptake, retention, and therapeutic efficacy in preclinical models.
Area of Science:
- Oncology
- Nuclear Medicine
- Biotechnology
Background:
- Human epidermal growth factor receptor 2 (HER2) overexpression is common in various cancers, including ovarian carcinoma.
- HER2 affibodies labeled with radioactive isotopes offer potential for targeted diagnosis and therapy.
- This research focuses on developing Iodine-131 labeled HER2 affibodies for targeted radionuclide therapy (TRNT) in HER2-positive ovarian cancer.
Purpose of the Study:
- To develop and evaluate 131I-labeled HER2 affibody (131I-YZHER2: V2) as a TRNT agent for HER2-positive ovarian cancer.
- To assess the radiochemical properties, pharmacokinetics, biodistribution, and therapeutic efficacy of 131I-YZHER2: V2 in preclinical models.
Main Methods:
- The YZHER2: V2 affibody targeting HER2 was synthesized and labeled with 131I using the chloramine T method.
- Radiochemical purity, stability, and affinity of 131I-YZHER2: V2 were evaluated in vitro.
- Pharmacokinetics, tumor uptake, biodistribution, and therapeutic effects were assessed in HER2-positive (SKOV-3) and HER2-negative (ID-8) mouse models.
Main Results:
- 131I-YZHER2: V2 was prepared with high yield (96.06% ± 1.26%) and good stability.
- The tracer demonstrated rapid uptake and retention in HER2-positive tumors, with favorable biodistribution and excretion pathways.
- Treatment with 131I-YZHER2: V2 resulted in reduced tumor growth and prolonged survival in mice with HER2-positive tumors.
Conclusions:
- 131I-YZHER2: V2 exhibits excellent properties for targeted radionuclide therapy.
- This agent shows significant potential as a novel TRNT for HER2-positive ovarian cancer.
- Further exploration of 131I-YZHER2: V2 for clinical application is warranted.
