The efficient radiosynthesis[KD([1] of biomolecules utilizing minute quantities of maleimide substrate is important for availability of novel peptide molecular imaging agents. We evaluated both 3-[18F]fluoropropane-1-thiol and 2-(2-(2-(2-[18F]fluoroethoxy)ethoxy)ethoxy)ethane-1-thiol ([18F]PEG4 thiol) as prosthetic groups for radiolabeling under physiological conditions. The precursor had benzoate protection of the thiol and an arylsulfonate leaving group. The [18F]fluoride displacement was fully automated on an Eckert & Ziegler synthesis system using standard Kryptofix 222/K2CO3 conditions. The intermediates were purified by HPLC to provide S-(3-[18F]fluoropropyl) benzothioate and [18F]PEG4 benzothioate, in yields of 37 – 47% and 28 – 35%, respectively. Purification of the intermediates reduced the amount of maleimide required for efficient coupling. The intermediates were isolated from the HPLC eluate using solid phase extraction and collected in ethanol. Treatment with NaOMe followed by acetic acid achieved deprotection. The desired maleimide substrate in acetonitrile or phosphate buffer was then added and incubated at room temperature for 15 to 30 min. The final product was purified on a separate HPLC. Maleimides utilized for the coupling reaction included phenylmaleimide, a dimeric RGDfK maleimide, and PSMA-617 maleimide. Isolated radiochemical yields of maleimide addition products based on starting [18F]fluoride ranged from 18 - 22 % in a synthesis time of &lt; 90 min.

3-[18F]fluoropropane-1-thiol and [18F]PEG4-1-thiol: Versatile prosthetic groups for radiolabeling maleimide functionalized peptides

2019 Spring National Meeting

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