Module-assisted one-pot synthesis of [~(18)F]SFB for radiolabeling proteins

摘要

The need of reliable production of N-succinimidyl 4-[~(18)F] fluorobenzoate ([~(18)F]SFB), a versatile ~(18)F-labeled prosthetic group for protein labeling, has increased dramatically due to the easy availability of proteins or their engineered derivatives for targeted molecular imaging. A module-assisted radiosynthesis of [~(18)F]SFB was developed using a three-step, one-pot procedure and ethyl 4-(trimethylammonium) benzoate triflate (1) as the starting material. The radiochemical transformations were carried out in a general-purpose, custom-made module and streamlined by an anhydrous deprotection strategy using t-BuOK/DMSO. After HPLC-purification, [~(18)F]SFB was synthesized in radiochemical yields of 20-30% (n > 10, not decay-corrected) and excellent radiochemical and chemical purities (>98%). The total synthesis and purification time required is ~90 min. Using the purified [~(18)F]SFB, three ~(18)F-labeled proteins, bovine serum albumin (BSA), chicken egg albumin (CEA) and transferrin, were synthesized in yields of 61.0-79.5%. The ~(18)F- Annexin V for apoptosis imaging was also produced in 5% radiolabeling yield and >95% radiochemical purity.