para‐Functionalized Aryl‐di‐tert‐butylfluorosilanes as Potential Labeling Synthons for 18F Radiopharmaceuticals

Abstract

Broad spectrum: Novel para‐functionalized aryl‐di‐tert‐butylfluorosilanes, p‐(tBu₂FSi)C₆H₄X (X=functional group), have been made available and broaden the spectrum of silicon‐based ¹⁸F acceptors (SiFAs) for potential PET applications. For example, the [¹⁸F]maleimido derivative 1 has been employed for the synthesis of [¹⁸F]1‐ labeled rat serum albumin (RSA), the applicability of which for PET has been verified by in vivo experiments. magnified image The syntheses of the functionalized triorganofluorosilanes tBu₂(p‐XC₆H₄)SiF (3 a, X=SH; 4 a, X=NCS; 4 b, X=NCO; 5, X=NC₄H₂O₂; 7, X=COOH; 8 a, X=COONC₄H₄O₂; 8 b, X=COOC₆F₅) are reported. These compounds display potential as silicon‐based fluoride acceptors (SiFAs). The molecular structures of compounds 5, 7, and 8 a have been determined by single‐crystal X‐ray diffraction studies. With the exception of compounds 8 a and 8 b, all of the compounds could be ¹⁸F‐labeled by isotopic exchange in good to high radiochemical yields (RCY) with good to excellent specific activities. As proof of applicability, the maleimido‐functionalized SiFA derivative 5, which is specific for thiol groups, has been used for the labeling of rat serum albumin (RSA) that had been derivatized with 2‐iminothiolane. The incorporation of [¹⁸F]5 into the derivatized RSA reached a maximum yield after 30 min at ambient temperature. After purification, the [¹⁸F]RSA was evaluated in a healthy rat by means of μPET and displayed an expedient in vivo stability over 180 min.