Fully automated synthesis of 4-[18F]fluorobenzylamine based on borohydride/NiCl2 reduction

Introduction: 4-[F-18]Fluorobenzylamine ([F-18]FBA) is an important building block for the synthesis of F-18-labeled compounds. Synthesis of [F-18]FBA usually involves application of strong reducing agents like LiAlH4 which is challenging to handle in automated synthesis units (ASUs). Therefore, alternative methods for the preparation of [F-18]FBA compatible with remotely-controlled syntheses in ASUs are needed. Methods: F-18]FBA was prepared in a remotely-controlled synthesis unit (GE TRACERlab (TM) FX) based on Ni(II)-mediated borohydride exchange resin (BER) reduction of 4[F-18]fluorobenzonitrile ([F-18]FBN). [F-18]FBA was used for the synthesis of novel thiol-reactive prosthetic group 4[F-18]fluorobenzyl)maleimide [F-18]FBM and Hsp90 inhibitor 17-(4-[F-18]fluorobenzylamino)-17-demethoxy-geldanamycin [F-18] GA. Results: [F-18]FBA could be prepared in high radiochemical yield greater than 80% (decay-corrected) within 60 min. In a typical experiment, 7.4 GBq of [F-18]FBA could be obtained in high radiochemical purity of greater than 95% starting from 10 GBq of cyclotron-produced n.c.a. [F-18]fluoride. [F-18]FBA was used for the preparation of 4-[F-18]fluorobenzyl)maleimide as a novel prosthetic group for labeling of thiol groups as demonstrated with tripeptide glutathione. [F-18]FBA was also used as building block for the syntheses of small molecules as exemplified by the preparation of Hsp90 inhibitor 17-(4-[F-18]fluorobenzylamino)-17-demethoxy-geldanamycin. Conclusion: The described remotely-controlled synthesis of [F-18]FBA will significantly improve the availability of [F-18]FBA as an important and versatile building block for the development of novel F-18-labeled compounds containing a fluorobenzylamine moiety. (C) 2013 Elsevier Inc. All rights reserved.