Direct Site-Specific Radiolabeling of an Affibody Protein with 4-[18F]Fluorobenzaldehyde via Oxime Chemistry

Abstract

Purpose-In this study, we introduce a methodology for preparing 18 F-labeled Affibody protein, specifically 18 F-Anti-HER2 dimeric Affibody (14 kDa), for in vivo imaging of HER2neu with positron emission tomography (PET). Conclusion-Site-specific 18 F-labeled Affibody against HER2 has been synthesized via chemoselective oxime formation between an aminooxy-functionalized Affibody and 18 Ffluorobenzaldehyde. The results have implications for radiolabeling of other affibodies and macromolecules and should also be important for advancing Affibody imaging with PET. Procedures-We

Incorporation of a Triglutamyl Spacer Improves the Biodistribution of Synthetic Affibody Molecules Radiofluorinated at the N-Terminus via Oxime Formation with 18F-4-Fluorobenzaldehyde

“…Unlike Affibody molecules labeled using residualizing radiometal labels 22,23,32,35 , the renal retention of 18 F-N-(4-fluorobenzylidine)oxime-labeled Affibody molecules is quite low (Figure 9). This is in agreement with data showing rapid clearance of radioactivity from kidneys for other Affibody molecules labeled with 18 F-N-(4-fluorobenzylidine)oxime 19,29,30 . This is a strong indication that the Experiments in tumor-bearing mice confirmed that 18 F-FBO-E 3 -PEP4313 can target HER2-expressing xenografts with high specificity (Figure 8).…”

“…In fact, 18 F-fluorobenzaldehyde conjugation has been used for labeling of recombinant dimeric 19 and monomeric 29 anti-HER2 Affibody molecules (after conjugation of 2-…”

Engineered High-Affinity Affibody Molecules Targeting Platelet-Derived Growth Factor Receptor β In Vivo

“…As Affibody molecules are devoid of cysteines, they allow homogenous site-specific labeling using maleimide chemistry after the introduction of a single cysteine for such labeling purposes. [35][36][37][38] Here we report the development of PDGFRβ-specific Affibody molecules aimed for in vivo tumor targeting. Development was performed in two steps-starting with selection of binders from a naive library of Affibody molecules, followed by an affinity maturation procedure.…”

Oxime formation for fluorine-18 labeling of peptides and proteins for positron emission tomography (PET) imaging: A review

“…In addition to [ 18 F]fluciclatide, a number of other peptides have been conjugated with [ 18 F]FBA [34,37,[41][42][43]. In general, the conjugations require low pH (e.g., pH 2.5 or below) and heating (60-70 8C) to improve reaction efficiency.…”