Chemoselective hydrazone formation between HYNIC-functionalized peptides and 18F-fluorinated aldehydes

摘要: Abstract Introduction Since the demand for 18 F-fluorinated peptides quantitative in vivo receptor imaging using PET has increased, a new chemoselective two-step F-labeling strategy based on hydrazone formation between an unprotected hydrazine-functionalized peptide and F-labeled aldehyde was developed. Methods First, 4-[ F]fluorobenzaldehyde ([ F]FB-CHO) prepared from 4-formyl- N , -trimethylanilinium triflate via direct no-carrier-added F-fluorination (dimethyl sulfoxide, 90°C, 5 min) purified by RP-HPLC. Hydrazone [ F]FB-CHO 6-hydrazinonicotinic acid (HYNIC) HYNIC-functionalized (HYNIC-d-Phe 1 )-Tyr 3 -Thr 8 -octreotide (HYNIC-Arg )-substance P evaluated with respect to dependence of radiochemical yield pH, precursor concentration temperature. The stability F]FB-CH=N-HYNIC-Tyr (NH 2 )-octreotide aqueous solution at various pH (4.0, 5.5 7.5) as well mouse blood (30 min p.i.) investigated. Results Yields were independent 0.5 5.5. Optimal labeling yields 85% obtained 2.1 mM 70°C 10 min. products stable 7.5 37°C, while more acidic media (pH 4.0) product slowly decomposed form up 31±2% within h. Metabolite studies showed no detectable degradation p.i.). Conclusions In conclusion, is fast straightforward radiolabeling method leading high under mild conditions. addition, it represents powerful versatile that applicable variety radionuclides precursors already available 99m Tc labeling.