[¹⁸F]FBAM and [¹⁸F]FBOM: Novel Thiol-reactive prosthetic groups derived from 4-[¹⁸F]fluorobenzaldehyde

The incorporation of ¹⁸F into peptides and proteins usually takes advantage of prosthetic groups, also referred to as bifunctional labeling agents. This approach comprises ¹⁸F incorporation into a small organic molecule capable of being linked to peptides and proteins under mild conditions.
Two new prosthetic groups derived from 4-[¹⁸F]fluorobenzaldehyde for the mild and selective conjugation to thiol-group containing biomacromolecules are described: N-[6-(4-[¹⁸F]fluorobenzylidene)aminooxyhexyl]-maleimide ([¹⁸F]FBAM) and 4-[¹⁸F]fluorobenzaldehyde-O-(2-{2-[2-(pyrol-2,5-dion-1-yl)ethoxy]ethoxy}ethyl)oxim ([¹⁸F]FBOM.
The aminooxy-functionalized labeling precursor for radiosynthesis of [¹⁸F]FBAM was prepared in a convenient three-step synthesis sequence in a total yield of 59%. The corresponding labeling precursor for the radiosynthesis of [¹⁸F]FBOM succeeded in a four-step reaction sequence in 14% total yield. Formation of the prosthetic groups [¹⁸F]FBAM and [¹⁸F]FBOM was achieved through condensation reaction with [¹⁸F]fluorobenzaldehyde to form the desired oximes in radiochemical yields of 20-30% ([¹⁸F]FBAM) and of 14-19% ([¹⁸F]FBOM), respectively. The syntheses were carried out in a remotely-controlled radiofluorination module allowing the convenient and reliable performance of the radiolabeling reactions. The radiochemical purity exceeded 95% and the specific activity ranged from 50 to 80 GBq/μmol. The total synthesis time was 70 to 80 min. The lipophilicity was determined to be logP=2.71 for [¹⁸F]FBAM and logP=0.84 for [¹⁸F]FBOM. Both prosthetic groups could successfully be used in the radiolabeling of thiol-group containing compounds such as glutathion, low density lipoproteins (LDL) and modified neurotensin derivatives.