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- Title
Direct site-specific radiolabeling of an Affibody protein with 4-[18F]fluorobenzaldehyde via oxime chemistry.
- Authors
Mohammad Namavari; Omayra Padilla De Jesus; Zhen Cheng; Abhijit De; Ernest Kovacs; Jelena Levi; Rong Zhang; Joshua Hoerner; Hans Grade; Faisal Syud; Sanjiv Gambhir; Namavari, Mohammad; Padilla De Jesus, Omayra; Cheng, Zhen; De, Abhijit; Kovacs, Ernest; Levi, Jelena; Zhang, Rong; Hoerner, Joshua K; Grade, Hans
- Abstract
<bold>Purpose: </bold>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).<bold>Procedures: </bold>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 degrees C for 15 min. The resulting 18F-labeled Affibody molecule was evaluated as a PET probe in xenograft models expressing HER2.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
POSITRON emission; POSITRON emission tomography; PROTEINS; ALDEHYDES; ORGANIC compounds; AMMONIUM; ACETATES
- Publication
Molecular Imaging & Biology, 2008, Vol 10, Issue 4, p177
- ISSN
1536-1632
- Publication type
journal article
- DOI
10.1007/s11307-008-0142-7