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. 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.