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

BACKGROUND: 9-(4-[F]fluoro-3-hydroxymethylbutyl) guanine ([F]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]FHBG presents many challenging laboratory requirements. AIM: To develop a simple one-pot fully-automated synthesis procedure of [F]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]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]FHBG with Sep-Pak purification was performed within a short synthesis time. The decay-uncorrected radiochemical yield of [F]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 theTK-transfected nude mice model indicated a much higher uptake of [F]FHBG in the TK-transfected tumor region than in the control tumor region. CONCLUSION: The automated synthesis of [F]FHBG is very easy to carry out using one-pot reactions combined with Sep-Pak purification. The synthetic [F]FHBG can be used for PET imaging and monitoring of in vivo herpes simplex virus type 1 TK gene expression.

[Radiosynthesis of peripheral benzodiazepine receptor radioligand [N-methyl-(11)C]PK 11195 as an imaging agent for positron emission tomography].

OBJECTIVE: To establish a protocol of automated synthesis of 1-(2-chlorophenyl)-N-[(11)C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ((11)C-PK11195) as the positron-emitter-labeled ligand for peripheral benzodiazepine receptor (PBR) using a commercial synthesizer and explore the quality control methods for the resulting product. METHODS: (11)C-methyl iodide ((11)C-CH(3)I) was synthesized via liquid-phase distillation approach using a (11)C-iodomethane synthesizer. (11)C-PK11195 was prepared by (11)C-methylation of 1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinoline carboxamide (N-demethyl-PK 11195) as the precursor with (11)C-CH(3)I and purified by semi-preparative reversed phase high performance liquid chromatography (HPLC). The radiochemical purity, chemical purity and stability of the product were evaluated by HPLC, and the toxicity was assessed in normal mice. The factors that affected (11)C-PK11195 synthesis were also studied. RESULTS: (11)C-PK11195 was successfully synthesized using the TracerLab FX(F-N) synthesizer. The synthesis time was about 35 min from the end of (11)C-carbon dioxide production by cyclotron to the end of (11)C-PK11195 synthesis (EOS), with a (11)C-methylation reaction time of 3-4 min. The uncorrected radiochemical yield for (11)C-methylation was (33-/+5)%. Analysis with radio-analytical HPLC showed a radiochemical purity and chemical purity of the product both exceeding 99%, with a specific radioactivity of 30-65 GBq/micromol at EOS (from the end of radionuclide production). The (11)C-PK11195 synthesized was radiochemically stable at room temperature and showed low toxicity in normal mice. CONCLUSION: The (11)C-PK11195 injection can be conveniently prepared using an automated synthesizer for clinical use in positron emission tomography.