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

摘要

The syntheses of the functionalized triorganofluorosilanes tBu(2)-(p-XC6H4)SiF (3a, X=SH; 4a, X= NCS; 4b. X=NCO; 5, X=NC4H2O2; 7, X=COOH; 8a. X=COONC4H4O2; 8b, X=COOC6F5) are reported. These compounds display potential as silicon-based fluoride acceptors (SiFAs). The molecular structures of compounds 5, 7, and 8a have been determined by single-crystal X-ray diffraction studies. With the exception of compounds 8a and 8b. all of the compounds could be F-18-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 [F-18]5 into the derivatized RSA reached a maximum yield after 30 min at ambient temperature. After purification, the [F-18]RSA was evaluated in a healthy rat by means of pPET and displayed an expedient in vivo stability over 180 min.