Abstract
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 99mTc 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 99mTc labelling. The cysteine can alternatively serve as a conjugation site of the chelator DOTA for indium labelling. The resulting 99mTc-and 111In-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 99mTc-labelled Affibody molecule had a fourfold lower kidney accumulation compared with the 111In-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).
Original language | English |
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Pages (from-to) | 1864-1873 |
Number of pages | 10 |
Journal | European Journal of Nuclear Medicine and Molecular Imaging |
Volume | 36 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2009 |
Externally published | Yes |
Keywords
- Affibody molecules
- HER2
- Imaging
- Peptide synthesis
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging