Scientific publications

A fully automated one pot synthesis of 9-(4-[18F]fluoro-3-hydroxymethylbutyl) guanine for gene therapy studies

Peñuelas I [SP], Boán JF, Martí-Climent JM [SP], Barajas MA, Narvaiza I, Satyamurthy N, Barrio JR, Richter JA [SP].
Department of Nuclear Medicine, University Hospital, University of Navarra School of Medicine, Pamplona, Spain

Magazine: Molecular Imaging and Biology

Date: Nov 1, 2002

Nuclear Medicine [SP]

PURPOSE
To develop a new fully-automated method for the synthesis of 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) amenable for its routine use in gene therapy monitoring studies.

PROCEDURES
A nuclear interface commercial synthesizer was substantially modified and adapted to the synthesis of the referred compound. After the fluorination reaction of the tosylate precursor, the intermediate product was purified by Solid Phase Extraction (SPE) before the hydrolysis. The final product was purified by semi-preparative high performance liquid chromatography (HPLC).

RESULTS
[18F]FHBG was obtained in 10-15% yield in 65 minutes including HPLC purification. The radiotracer was > 99% chemically and radiochemically pure, sterile and free from pyrogens. The synthesized compound was shown to accumulate in thymidine kinase (tk) expressing cells both in cell culture, and in laboratory animals infected with an adenoviral vector containing the herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene.

CONCLUSIONS
This new procedure facilitates the compliance with the applicable regulatory guidelines for positron emission tomography (PET) radiopharmaceuticals and will assist the clinical application of [18F]FHBG-PET as a noninvasive way to monitor gene therapy in humans.

CITATION  Mol Imaging Biol. 2002 Nov;4(6):415-24

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