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. 2012 Nov;39(8):1182-8.
doi: 10.1016/j.nucmedbio.2012.06.008. Epub 2012 Jul 18.

An improved strategy for the synthesis of [¹⁸F]-labeled arabinofuranosyl nucleosides

Hanwen Zhang  1 , Melchor V Cantorias, NagaVaraKishore Pillarsetty, Eva M Burnazi, Shangde Cai, Jason S Lewis
Affiliations

An improved strategy for the synthesis of [¹⁸F]-labeled arabinofuranosyl nucleosides

Hanwen Zhang et al. Nucl Med Biol. 2012 Nov.

Abstract

The expression of the herpes simplex virus type-1 thymidine kinase (HSV1-tk) gene can be imaged efficaciously using a variety of 2'-[(18)F]fluoro-2'-deoxy-1-b-D-arabinofuranosyl-uracil derivatives [[(18)F]-FXAU, X=I(iodo), E(ethyl), and M(methyl)]. However, the application of these derivatives in clinical and translational studies has been impeded by their complicated and long syntheses (3-5h). To remedy these issues, in the study at hand we have investigated whether microwave or combined catalysts could facilitate the coupling reaction between sugar and nucleobase and, further, have probed the feasibility of establishing a novel approach for [(18)F]-FXAU synthesis. We have demonstrated that the rate of the trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed coupling reaction between the 2-deoxy-sugar and uracil derivatives at 90 °C can be significantly accelerated by microwave-driven heating or by the addition of Lewis acid catalyst (SnCl(4)). Further, we have observed that the stability of the α- and β-anomers of [(18)F]-FXAU derivatives differs during the hydrolysis step. Using the microwave-driven heating approach, overall decay-corrected radiochemical yields of 19%-27% were achieved for [(18)F]-FXAU in 120min at a specific activity of >22MBq/nmol (595Ci/mmol). Ultimately, we believe that these high yielding syntheses of [(18)F]-FIAU, [(18)F]-FMAU and [(18)F]-FEAU will facilitate routine production for clinical applications.

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Figures

Figure 1
Figure 1
HPLC monitoring of coupling reaction between 18F-sugar and 5-Iodo-uracil, heated using microwave for 15 min. Method 1 (details in method section), 0.05%TFA in water/AcCN as mobile phase. Red line: sample was from radiosynthesis; Black line: sample from the synthesis of cold 3.
Figure 2
Figure 2
A typical HPLC chromatogram showing purification of [18F]-FIAU using a semi-preparative HPLC system. Red line: radioactive signal from radio-detector (Rad); Black line: UV signal from UV detector (UV) @ 254 nm.
Figure 3
Figure 3
Quality control analysis of [18F]-FIAU with analytical HPLC system. A) [18F]-FIAU coinjected with cold standard, FIAU; B) [18F]-FIAU. Red line: radioactive signal from radio-detector (Rad); Black line: UV signal from UV detector (UV) @ 280 nm.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
See this image and copyright information in PMC

References

    1. Gelovani Tjuvajev J, Blasberg RG. In vivo imaging of molecular-genetic targets for cancer therapy. Cancer Cell. 2003;3:327–32. - PubMed
    1. Herschman HR. Noninvasive imaging of reporter gene expression in living subjects. Adv Cancer Res. 2004;92:29–80. - PubMed
    1. Serganova I, Blasberg R. Reporter gene imaging: potential impact on therapy. Nucl Med Biol. 2005;32:763–80. - PubMed
    1. Doubrovin M, Ponomarev V, Beresten T, Balatoni J, Bornmann W, Finn R, et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci U S A. 2001;98:9300–5. - PMC - PubMed
    1. Ponomarev V, Doubrovin M, Lyddane C, Beresten T, Balatoni J, Bornman W, et al. Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo. Neoplasia. 2001;3:480–8. - PMC - PubMed

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