Rapid Synthesis of Aldehyde and Maleimide Functionalized Fluorine-18 Labeled Prosthetic Group using ‘Radio-fluorination on the Sep-Pak’ Method

Objectives: Our objective is to expand the scope of our recently published fluorine-18 labeling method, ‘Radio-fluorination on the Sep-Pak’ for an improved, optimized, simple, reproducible synthesis of fluorine-18 labeled prosthetic groups.Methods: Fluorine-18 radiolabeled 6-fluoronicotinaldehyde was prepared quickly by passing the quaternary ammonium triflate precursor through a fluorine-18 trapped Sep-Pak (PS-HCO₃) as recently reported by us [1]. The [¹⁸F]fluoronicotinaldehyde was then conjugated with 1-(6-(aminooxy)hexyl)-1H-pyrrole-2,5-dione at 80 ºC for 5 min to prepare the fluorine-18 labeled maleimide functionalized prosthetic group, 6-[¹⁸F]fluoronicotinaldehyde O-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexyl) oxime, 6-[¹⁸F]FPyMHO. Results: We have successfully prepared 6-[¹⁸F]fluoronicotinaldehyde on the Sep-Pak. Fluorination yield of this current method with a shorter synthesis time is comparable to the literature method [2]. The radiochemical yield was 85 ± 3% (uncorrected, n = 6) with a radiochemical purity of >98%. Using 6-[¹⁸F]fluoronicotinaldehyde, another useful site specific thiol reactive prosthetic group, 6-[¹⁸F]FPyMHO, was synthesized. The overall radiochemical yield and purity of 6-[¹⁸F]FPyMHO were 44±7% (n = 8, uncorrected) and > 90 % respectively in 30 min synthesis time. Conclusions: The current Sep-Pak method not only improves the overall radiochemical yield of 6-[¹⁸F]FPyMHO but also significantly reduces the synthesis time (from 60-90 min to 30 min) when compared with literature methods for the synthesis of similar prosthetic groups [3]. This simple and fast radiolabeling procedure at room temperature without azeotropic drying of fluorine-18 has potential applications in the preparation of other useful fluorine-18 labeled synthons. Research Support: This study was funded by the intramural program of the National Institutes of Health. References: [1] Basuli F, Zhang X, Jagoda EM, Choyke PL, and Swenson RE. Nuclear Medicine and Biology, 2016;43:770-772. [2] Kügler F, Ermert J, and Coenen HH. Labeling of benzodioxin piperazines with fluorine-18 as prospective radioligands for selective imaging of dopamine D4 receptors. Journal of Labelled Compounds and Radiopharmaceuticals 2013;56:609-618. [3] Moore TM, Akula MR, and Kabalka GW. Fluorine-18 Radiochemistry: A Novel Thiol-Reactive Prosthetic Group, [¹⁸F]FBAMPy. Natural Science 2016;8:1-7.