Purpose: The purpose of this study was to design and evaluate a novel platform for labelling of Affibody molecules, enabling both recombinant and synthetic production and site-specific labelling with (99m)Tc or trivalent radiometals.
Methods: The HER2-specific Affibody molecule PEP05352 was made by peptide synthesis. The chelator sequence SECG (serine-glutamic acid-cysteine-glycine) was anchored on the C-terminal to allow (99m)Tc labelling. The cysteine can alternatively serve as a conjugation site of the chelator DOTA for indium labelling. The resulting (99m)Tc- and (111)In-labelled Affibody molecules were evaluated both in vitro and in vivo.
Results: Both conjugates retained their capacity to bind to HER2 receptors in vitro and in vivo. The tumour to blood ratio in LS174T xenografts was 30 at 4 h post-injection for both conjugates. Biodistribution data showed that the (99m)Tc-labelled Affibody molecule had a fourfold lower kidney accumulation compared with the (111)In-labelled Affibody molecule while the accumulation in other organs was similar. Gamma camera imaging of the conjugates could clearly visualise the tumours 4 h after injection.
Conclusion: Incorporation of the C-terminal SECG sequence in Affibody molecules provides a general multifunctional platform for site-specific labelling with different nuclides (technetium, indium, gallium, cobalt or yttrium) and for a flexible production (chemical synthesis or recombinant).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00259-009-1176-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
DGCR2 targeting affibody molecules for delivery of drugs and imaging reagents to human beta cells.
Sci Rep
January 2025
Science For Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
A distinctive feature of both type 1 and type 2 diabetes is the waning of insulin-secreting beta cells in the pancreas. New methods for direct and specific targeting of the beta cells could provide platforms for delivery of pharmaceutical reagents. Imaging techniques such as Positron Emission Tomography (PET) rely on the efficient and specific delivery of imaging reagents, and could greatly improve our understanding of diabetes etiology as well as providing biomarkers for viable beta-cell mass in tissue, in both pancreas and in islet grafts.
View Article and Find Full Text PDFExpression-Dependent Tumor Pretargeting via Engineered Avidity.
Mol Pharm
January 2025
Department of Biomedical Engineering, University of Minnesota-Twin Cities, Minneapolis, Minnesota 55455, United States.
Selective delivery of therapeutic modalities to tumor cells via binding of tumor-selective cell-surface biomarkers has empowered substantial advances in cancer treatment. Yet, tumor cells generally lack a truly specific biomarker that is present in high density on tumor tissue while being completely absent from healthy tissue. Rather, low but nonzero expression in healthy tissues results in on-target, off-tumor activity with detrimental side effects that constrain the therapeutic window or prevent use altogether.
View Article and Find Full Text PDFFirst-in-human Study of ABY-029, a Novel Fluorescent Peptide that Targets Epidermal Growth Factor Receptor, Applied to Soft-Tissue Sarcomas.
Mol Cancer Ther
December 2024
Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States.
ABY-029, an anti-epidermal growth factor receptor (EGFR) Affibody® molecule conjugated to IRDye 800CW, recently underwent first-in-human testing in soft-tissue sarcoma (STS). FDA Exploratory Investigational New Drug status was obtained for the Phase 0 clinical trial in which study objectives were to determine whether biological variance ratio (BVR) of 10 was achievable, fluorescence intensity correlated with EGFR expression, and doses were well tolerated. Patients (N=12) with STS were recruited based on positive EGFR immunohistochemical staining of diagnostic biopsies.
View Article and Find Full Text PDFNovel affibody molecules targeting the AXL extracellular structural domain for molecular imaging and targeted therapy of gastric cancer.
Gastric Cancer
December 2024
Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, People's Republic of China.
Gastric cancer (GC) has a poor prognosis and high mortality because it is often diagnosed at an advanced stage. Targeted therapeutics are considered an important class for advanced GC treatment. However, the fewer effective therapeutic targets and the poor coverage of the GC population limit the use of GC targeted therapies.
View Article and Find Full Text PDFHER2-Targeted Affibody Molecule 99mTc-ABH2 for Imaging HER2 Expression in Breast Cancer.
Clin Nucl Med
January 2025
From the Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China.
Purpose: Accuracy in in vivo assessment of human epidermal growth factor receptor type 2 (HER2) status is crucial for predicting the response to HER2-targeted therapies in breast cancer. This study assessed the safety, feasibility, and diagnostic accuracy of 99mTc-ABH2, a reengineered affibody molecule with radionuclide labeling, for HER2 expression in breast cancer using SPECT/CT imaging, compared with 18F-FDG PET/CT.
Patients And Methods: Thirty-six patients suspected of primary breast cancer were enrolled in this prospective, single-center study from March to July in 2023.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!