Abstract
Purpose
In this study, we introduce a methodology for preparing 18F-labeled Affibody protein, specifically 18F-Anti-HER2 dimeric Affibody (14 kDa), for in vivo imaging of HER2neu with positron emission tomography (PET).
Procedures
We have used 4-[18F]fluorobenzaldehyde as a synthon to prepare 18F-Anti-HER2 Affibody. Aminooxy-functionalized Affibody (Anti-HER2-ONH2) was incubated with 4-[18F]fluorobenzaldehyde in ammonium acetate buffer at pH 4 in the presence of methanol at 70°C for 15 min. The resulting 18F-labeled Affibody molecule was evaluated as a PET probe in xenograft models expressing HER2.
Results
We have successfully prepared 18F-Anti-HER2 dimeric Affibody (14 kDa), N-(4-[18F]fluorobenzylidine)oxime-Anti-HER2 Affibody, [18F]FBO-Anti-HER2, in 26–30% radiochemical yields (decay corrected). High-contrast small-animal PET images with relatively moderate tumor uptake (1.79 ± 0.40% ID/g) were observed for the 18F-Anti-HER2 Affibody.
Conclusion
Site-specific 18F-labeled Affibody against HER2 has been synthesized via chemoselective oxime formation between an aminooxy-functionalized Affibody and 18F-fluorobenzaldehyde. The results have implications for radiolabeling of other affibodies and macromolecules and should also be important for advancing Affibody imaging with PET.
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Acknowledgment
This work was supported, in part, by Medical Diagnostics, GE Healthcare, National Cancer Institute (NCI) Small Animal Imaging Resource Program (SAIRP) grant R24 CA93862, and NCI In Vivo Cellular Molecular Imaging Center (ICMIC) grant P50 CA114747 (SSG). We also thank Dr. David Dick for [18F] production, Dr. Frederick T. Chin for modification of a GE TRACERlab FX-FN synthetic module for radiosynthesis of 4-[18F]FBA, and Dr. Alan Cuthbertson and Dr. Alex Gibson of GE Healthcare for their review of the manuscript.
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Namavari, M., Padilla De Jesus, O., Cheng, Z. et al. Direct Site-Specific Radiolabeling of an Affibody Protein with 4-[18F]Fluorobenzaldehyde via Oxime Chemistry. Mol Imaging Biol 10, 177–181 (2008). https://doi.org/10.1007/s11307-008-0142-7
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DOI: https://doi.org/10.1007/s11307-008-0142-7