Efficient synthesis of a fluorine-18 labeled biotin derivative

IntroductionThe natural occurring vitamin biotin, also known as vitamin H or vitamin B7, plays a major role in various metabolic reactions. Caused by its high binding affinity to the protein avidin with a dissociation constant of about 10- 15 M the biotin-avidin system was extensively examined for multiple applications. We have synthesized a fluorine-18 labeled biotin derivative [18F]4 for a potential application in positron emission tomography (PET).MethodsMesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [18F]4 was successfully synthesized by a nucleophilic radiofluorination of precursor 3. A biodistribution study by means of small-animal PET imaging in wt-mice was performed and serum stability was examined.ResultsCompound [18F]4 was obtained from precursor compound 3 with an average specific activity of 16 GBq/μmol within 45 min and a radiochemical yield of 45 ± 5% (decay corrected). [18F]4 demonstrated only negligible decomposition in human serum. A qualitative binding study revealed the high affinity of the synthesized biotin derivative to avidin. Blocking experiments with native biotin showed that binding was site-specific. Biodistribution studies showed that [18F]4 was cleared quickly and efficiently from the body by hepatobiliary and renal elimination.ConclusionAn efficient synthesis for [18F]4 was established. In vivo characteristics were determined and demonstrated the pharmacokinetic behaviour of [18F]4.