A simplified one-pot automated synthesis of [18F]FHBG for imaging reporter gene expression

Background 9-(4-[F-18]fluoro-3-hydroxymethylbutyl) guanine ([F-18]FHBG) has been used as a reporter probe to image the expression of the herpes simplex virus type 1 thymidine kinase (TK) reporter gene in living organisms with positron emission tomography (PET). However, the routine production of [F-18]FHBG presents many challenging laboratory requirements. Aim To develop a simple one-pot fully-automated synthesis procedure of [F-18]FHBG amenable for its routine use in reporter gene expression PET imaging studies. Methods A TRACERlab FXF-N synthesizer was substantially modified and adapted to the synthesis of [F-18]FHBG through the two-step one-pot procedure. After the fluorination reaction of the tosylate precursor and the hydrolysis of the intermediate product in the same reaction vessel, the final product was purified by Sep-Pak cartridges instead of the high performance liquid chromatography system. Results The fully automated synthesis of [F-18]FHBG with Sep-Pak purification was performed within a short synthesis time. The decay-uncorrected radiochemical yield of [F-18]FHBG was 8-14% (n = 10), the radiochemical purity was more than 99%, and the entire synthesis time was less than 40 min. In addition, the PET image of the TK-transfected nude mice model indicated a much higher uptake of [F-18]FHBG in the TK-transfected tumor region than in the control tumor region. Conclusion The automated synthesis of [F-18]FHBG is very easy to carry out using one-pot reactions combined with Sep-Pak purification. The synthetic [F-18]FHBG can be used for PET imaging and monitoring of in vivo herpes simplex virus type 1 TK gene expression. Nucl Med Commun 31: 211-216 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.