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

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