Site-selective radiolabeling of peptides by ¹⁸F-fluorobenzoylation with [¹⁸F]SFB in solution and on solid phase - a comparative study

Peptides labeled with short-lived positron-emitting radionuclides are of outstanding interest as probes for molecular imaging by positron emission tomography (PET). Herein, the site-selective incorporation of fluorine-18 into lysine-containing peptides using the prosthetic labeling agent N-succinimidyl 4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) is described. The reaction of [¹⁸F]SFB with four biologically relevant resin-bound peptides was studied and optimized. For comparison, each peptide was ¹⁸F-fluorobenzoylated in solution under different conditions and the product distribution was analyzed confirming the advantages of the solid phase approach. The method's feasibility for selective radiolabeling either at the N-terminus or at the lysine side chain was demonstrated. Labeling on solid phase with ¹⁸F]SFB resulted in crude ¹⁸F-fluorobenzoylpeptides whose radiochemical purities were typically greater than 90 % and that could be prepared in synthesis times from 65 to 76 min.