Development of a positron emission tomography radiopharmaceutical for imaging thymidine kinase gene expression: Synthesis and in vitro evaluation of 9-{3-[18F] Fluoro-1-hydroxy-2-propoxymethyl guanine

Bioorganic & Medicinal Chemistry Letters
1997.0

Abstract

9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine (FHPG) 2 has been labeled with fluorine-18 and evaluated in vitro as a potential radiotracer for mapping gene expression in vivo with positron emission tomography (PET). Recently new approaches of gene therapy have been proposed for the treatment of various human diseases. Among them, a promising gene therapy protocol for cancer consists of the transduction of neoplastic cells with the herpes simplex virus thymidine kinase gene (HSV-tk) which renders transduced cells sensitive to the lethal effect of antiviral agent such as ganciclovir (DHPG) 1. Positron emission tomography (PET) with adapted radiotracers represents a potential tool to determine the in vivo level of HSV-tk expression and to establish the optimal protocol of gene and ganciclovir administration in human. Until now, only a few molecules with potential applications to PET have appeared in the literature. 5-Iodo-2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil (FIAU) 2,3 and 8-fluoro-9-[(2-hydroxyethoxy)methyl]guanine 4 have been investigated as possible candidates for PET studies. Synthesis of 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine 2 was recently achieved 5,6 and we report here our preliminary results with this molecule.

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