High yield two-steps method of synthesizing 18F-FB-HYNIC-peptides

Objectives 18F-labeled peptides show great potential in PET receptor imaging, 18F-SFB is a popular compound used in 18F-peptides labeling, but it is only sensitive to peptides with e-NH2. 18F-FBEM is also explored based on 18F-SFB, for peptides with thiol. But these labeling methods are complicated and difficult to achieve automatic production. Researchers also explored 4-[18F] Fluorobenzaldehyde to achieve two-steps method to synthesis 18F-FBOA-peptides. Here we intend to explore a simple and high yield method by 4-[18F] Fluorobenzaldehyde and HYNIC-peptides, because HYNIC-peptides are widely used in 99mTc peptides labeling.

Methods At first we synthesized 4-formyl-N,N,N-trimethylanilinium triflate by 4-N,N-dimethylaminobenzaldehyde and methyltrifluoromethanesulfonate. Then methyltrifluoromethanesulfonate was labeled by [KÌ2.2.2+]18F- in DMSO and separated by preparative HPLC or solid-phase cartridges. 4-[18F]fluorobenzaldehyde was collected. At last we mixed 4-[18F]fluorobenzaldehyde with HYNIC-RGD which was dissolved in 1ml NaOAc(pH-4.5). After 10 min heated in 90°C, mixture was separated in preparative HPLC, and 18F-FB-HYNIC-RGD was achieved.

Results We successfully synthesized 18F-FB-HYNIC-RGD by two-steps method. 4-[18F] Fluorobenzaldehyde was synthesized ten times and the average RCY is 75±5%(decay corrected), 18F-FB-HYNIC-RGD was synthesized five times by 4-[18F] Fluorobenzaldehyde, and the average RCY is 85±10% (decay corrected).

Conclusions We explored a simple two-steps method to synthesis 18F-FB-HYNIC-peptides. It is easy to achieve automatic synthesis in GE TRACERlab FX FN module. The radiochemical yield is very high. It benefits 18F-labeled peptides clinical application