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Updated: Feb 20, 2026
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Evaluation of a radiocobalt-labelled affibody molecule for imaging of human epidermal growth factor receptor 3
Maria Rosestedt1, Ken G Andersson2, Bogdan Mitran1
1Division of Molecular Imaging, Department of Medicinal Chemistry, Uppsala University, 751 83 Uppsala, Sweden.
Abstract:
The human epidermal growth factor receptor 3 (HER3) is involved in the development of cancer resistance towards tyrosine kinase-targeted therapies. Several HER3‑targeting therapeutics are currently under clinical evaluation. Non-invasive imaging of HER3 expression could improve patient management. Affibody molecules are small engineered scaffold proteins demonstrating superior properties as targeting probes for molecular imaging compared with monoclonal antibodies. Feasibility of in vivo HER3 imaging using affibody molecules has been previously demonstrated. Preclinical studies have shown that the contrast when imaging using anti-HER3 affibody molecules can be improved over time. We aim to develop an agent for PET imaging of HER3 expression using the long-lived positron-emitting radionuclide cobalt-55 (55Co) (T1/2=17.5 h). A long-lived cobalt isotope 57Co was used as a surrogate for 55Co in this study. The anti-HER3 affibody molecule HEHEHE-ZHER3-NOTA was labelled with radiocobalt with high yield, purity and stability. Biodistribution of 57Co-HEHEHE-ZHER3-NOTA was measured in mice bearing DU145 (prostate carcinoma) and LS174T (colorectal carcinoma) xenografts at 3 and 24 h post injection (p.i.). Tumour-to-blood ratios significantly increased between 3 and 24 h p.i. (p<0.05). At 24 h p.i., tumour-to-blood ratios were 6 for DU145 and 8 for LS174T xenografts, respectively. HER3‑expressing xenografts were clearly visualized in a preclinical imaging setting already 3 h p.i., and contrast further improved at 24 h p.i. In conclusion, the radiocobalt-labelled anti-HER3 affibody molecule, HEHEHE-ZHER3-NOTA, is a promising tracer for imaging of HER3 expression in tumours.
Insights
A novel radiocobalt-labeled anti-HER3 affibody molecule, HEHEHE-ZHER3-NOTA, shows promise for PET imaging. This tracer effectively visualizes HER3-expressing tumors, improving patient management for cancer therapies.
Area of Science:
- Oncology
- Molecular Imaging
- Radiochemistry
Background:
- Human epidermal growth factor receptor 3 (HER3) is implicated in cancer resistance to targeted therapies.
- Targeting HER3 is a focus for new cancer treatments, necessitating methods for non-invasive expression imaging.
- Affibody molecules offer advantages over antibodies for molecular imaging probes.
Purpose of the Study:
- To develop a positron emission tomography (PET) imaging agent for HER3 expression using the long-lived radionuclide cobalt-55 (55Co).
- To evaluate the feasibility and efficacy of a radiocobalt-labeled anti-HER3 affibody molecule for preclinical HER3 imaging.
Main Methods:
- An anti-HER3 affibody molecule, HEHEHE-ZHER3-NOTA, was labeled with a surrogate radiocobalt isotope (57Co).
- Biodistribution studies were conducted in mice with HER3-expressing xenografts (DU145 and LS174T).
- Imaging was performed at 3 and 24 hours post-injection to assess tumor visualization and contrast.
Main Results:
- The radiolabeled affibody, 57Co-HEHEHE-ZHER3-NOTA, was produced with high yield, purity, and stability.
- Tumor-to-blood ratios increased significantly between 3 and 24 hours post-injection (6 for DU145, 8 for LS174T at 24h).
- HER3-expressing xenografts were clearly visualized, with improved contrast over time.
Conclusions:
- The radiocobalt-labeled anti-HER3 affibody molecule HEHEHE-ZHER3-NOTA is a viable PET imaging tracer.
- This agent demonstrates potential for non-invasive imaging of HER3 expression in tumors.
- Improved imaging contrast over time suggests clinical utility for patient management in HER3-targeted therapies.
