Efficient synthesis of a fluorine-18 labeled biotin derivative

Introduction: The natural occurring vitamin biotin, also known as vitamin Hot vitamin B-7, 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 [F-18]4 for a potential application in positron emission tomography (PET). Methods: Mesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [F-18]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. Results: Compound [F-18]4 was obtained from precursor compound 3 with an average specific activity of 16 GBq/mu mol within 45 min and a radiochemical yield of 45 +/- 5% (decay corrected). [F-18]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 [F-18]4 was cleared quickly and efficiently from the body by, hepatobiliary and renal elimination. Conclusion: An efficient synthesis for [F-18]4 was established. In vivo characteristics were determined and demonstrated the pharmkokinetic behaviour of [F-18]4. (C) 2012 Elsevier inc. All rights reserved.