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Targeting against epidermal growth factor receptors. Cellular processing of astatinated EGF after binding to cultured
Anna Orlova1, Anna Sjöstrom, Ondrej Lebeda
1Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. Anna.Orlova@bms.uu.se
Background:
The alpha-emitting nuclide 211At is of great interest for radionuclide therapy when coupled to a tumor-targeting biomolecule, e.g. epidermal growth factor (EGF) the receptors of which are overexpressed in many malignancies. However, almost no information concerning the cellular processing of astatinated targeting agents is available.
Materials And Methods:
We indirectly astatinated EGF ([211At]-benzoate-EGF) and studied its cellular processing in A-431 carcinoma cells in comparison with data concerning [125I]-benzoate-EGF.
Results:
The biological half-life of astatine (3.5 h) was longer than the half-life of the iodine label (1.5 h). The increase of the half-life was due to longer retention of the internalised astatine radioactivity. The maximum accumulation for the astatine label occurred later (4-6h) than that for the iodine label (2-4h), indicating a slower excretion of astatine that was confirmed in experiment with 211At/1251-benzoate-EGF.
Conclusion:
The long retention of astatine might be advantageous for radionuclide therapy.
Insights
Astatine-211 labeled EGF showed longer cellular retention than iodine-125, suggesting potential benefits for targeted radionuclide therapy in cancer treatment.
Area of Science:
- Nuclear medicine
- Radiopharmaceutical chemistry
- Oncology
Background:
- Alpha-emitting nuclide 211At is promising for radionuclide therapy.
- Targeting biomolecules like EGF are overexpressed in malignancies.
- Limited data exists on cellular processing of astatinated agents.
Purpose of the Study:
- To investigate the cellular processing of astatinated EGF ([211At]-benzoate-EGF).
- To compare its behavior with iodine-125 labeled EGF ([125I]-benzoate-EGF).
Main Methods:
- Indirect astatination of EGF using [211At]-benzoate.
- Cellular processing study in A-431 carcinoma cells.
- Comparative analysis with [125I]-benzoate-EGF.
Main Results:
- Astatine label ([211At]) exhibited a longer biological half-life (3.5 h) than iodine ([125I]) (1.5 h).
- Longer retention of internalized astatine radioactivity contributed to the increased half-life.
- Maximum accumulation of astatine occurred later (4-6h) compared to iodine (2-4h), indicating slower excretion.
Conclusions:
- The extended cellular retention of astatine suggests its potential advantage for radionuclide therapy.
- Further research into astatinated agents for cancer treatment is warranted.
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