TY - JOUR
T1 - Chemoselective hydrazone formation between HYNIC-functionalized peptides and 18F-fluorinated aldehydes
AU - Bruus-Jensen, Kjerstin
AU - Poethko, Thorsten
AU - Schottelius, Margret
AU - Hauser, Andrea
AU - Schwaiger, Markus
AU - Wester, Hans Jürgen
PY - 2006/2
Y1 - 2006/2
N2 - Introduction: Since the demand for 18F-fluorinated peptides for quantitative in vivo receptor imaging using PET has increased, a new chemoselective two-step 18F-labeling strategy based on hydrazone formation between an unprotected hydrazine-functionalized peptide and an 18F-labeled aldehyde was developed. Methods: First, 4-[ 18F]fluorobenzaldehyde ([18F]FB-CHO) was prepared from 4-formyl-N,N,N-trimethylanilinium triflate via direct no-carrier-added 18F-fluorination (dimethyl sulfoxide, 90°C, 5 min) and purified by RP-HPLC. Hydrazone formation between [18F]FB-CHO and 6-hydrazinonicotinic acid (HYNIC) and the unprotected HYNIC-functionalized peptides (HYNIC-d-Phe1)-Tyr3-Thr8-octreotide and (HYNIC-Arg1)-substance P was evaluated with respect to the dependence of radiochemical yield on pH, precursor concentration and temperature. The stability of [18F]FB-CH=N-HYNIC-Tyr 3-Thr8(NH2)-octreotide in aqueous solution at various pH (4.0, 5.5 and 7.5) as well as the in vivo stability of [ 18F]FB-CH=N-HYNIC-Tyr3-Thr8-octreotide in mouse blood (30 min p.i.) was investigated. Results: Yields of the hydrazone formation were independent of pH between pH 0.5 and 5.5. Optimal labeling yields of 85% were obtained with a precursor concentration of 2.1 mM at 70°C for 10 min. The labeling products were stable at pH 7.5 at 37°C, while in more acidic media (pH 4.0) the product slowly decomposed to form up to 31±2% [18F]FB-CHO within 5 h. Metabolite studies showed no detectable degradation of [18F]FB-CH=N-HYNIC-Tyr3-Thr 8-octreotide in mouse blood (30 min p.i.). Conclusions: In conclusion, chemoselective hydrazone formation between unprotected HYNIC-functionalized peptides and [18F]FB-CHO is a fast and straightforward radiolabeling method leading to high yields under mild acidic conditions. In addition, it represents a powerful and versatile radiolabeling strategy that is applicable to a variety of radionuclides and peptide precursors already available for 99mTc labeling.
AB - Introduction: Since the demand for 18F-fluorinated peptides for quantitative in vivo receptor imaging using PET has increased, a new chemoselective two-step 18F-labeling strategy based on hydrazone formation between an unprotected hydrazine-functionalized peptide and an 18F-labeled aldehyde was developed. Methods: First, 4-[ 18F]fluorobenzaldehyde ([18F]FB-CHO) was prepared from 4-formyl-N,N,N-trimethylanilinium triflate via direct no-carrier-added 18F-fluorination (dimethyl sulfoxide, 90°C, 5 min) and purified by RP-HPLC. Hydrazone formation between [18F]FB-CHO and 6-hydrazinonicotinic acid (HYNIC) and the unprotected HYNIC-functionalized peptides (HYNIC-d-Phe1)-Tyr3-Thr8-octreotide and (HYNIC-Arg1)-substance P was evaluated with respect to the dependence of radiochemical yield on pH, precursor concentration and temperature. The stability of [18F]FB-CH=N-HYNIC-Tyr 3-Thr8(NH2)-octreotide in aqueous solution at various pH (4.0, 5.5 and 7.5) as well as the in vivo stability of [ 18F]FB-CH=N-HYNIC-Tyr3-Thr8-octreotide in mouse blood (30 min p.i.) was investigated. Results: Yields of the hydrazone formation were independent of pH between pH 0.5 and 5.5. Optimal labeling yields of 85% were obtained with a precursor concentration of 2.1 mM at 70°C for 10 min. The labeling products were stable at pH 7.5 at 37°C, while in more acidic media (pH 4.0) the product slowly decomposed to form up to 31±2% [18F]FB-CHO within 5 h. Metabolite studies showed no detectable degradation of [18F]FB-CH=N-HYNIC-Tyr3-Thr 8-octreotide in mouse blood (30 min p.i.). Conclusions: In conclusion, chemoselective hydrazone formation between unprotected HYNIC-functionalized peptides and [18F]FB-CHO is a fast and straightforward radiolabeling method leading to high yields under mild acidic conditions. In addition, it represents a powerful and versatile radiolabeling strategy that is applicable to a variety of radionuclides and peptide precursors already available for 99mTc labeling.
KW - Chemoselective
KW - F
KW - Hydrazone formation
KW - PET
KW - Peptide
KW - Radiohalogenation
UR - http://www.scopus.com/inward/record.url?scp=33644938767&partnerID=8YFLogxK
U2 - 10.1016/j.nucmedbio.2005.10.010
DO - 10.1016/j.nucmedbio.2005.10.010
M3 - Article
C2 - 16546671
AN - SCOPUS:33644938767
SN - 0969-8051
VL - 33
SP - 173
EP - 183
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 2
ER -
