An improved strategy for the synthesis of [ 18F]-labeled arabinofuranosyl nucleosides Journal Article
| Authors: | Zhang, H.; Cantorias, M. V.; Pillarsetty, N.; Burnazi, E. M.; Cai, S.; Lewis, J. S. |
| Article Title: | An improved strategy for the synthesis of [ 18F]-labeled arabinofuranosyl nucleosides |
| Abstract: | The expression of the herpes simplex virus type-1 thymidine kinase (HSV1-tk) gene can be imaged efficaciously using a variety of 2'-[ 18F]fluoro-2'-deoxy-1-b-D-arabinofuranosyl-uracil derivatives [[ 18F]-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 [ 18F]-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 [ 18F]-FXAU derivatives differs during the hydrolysis step. Using the microwave-driven heating approach, overall decay-corrected radiochemical yields of 19%-27% were achieved for [ 18F]-FXAU in 120min at a specific activity of >22MBq/nmol (595Ci/mmol). Ultimately, we believe that these high yielding syntheses of [ 18F]-FIAU, [ 18F]-FMAU and [ 18F]-FEAU will facilitate routine production for clinical applications. © 2012 Elsevier Inc.. |
| Keywords: | unclassified drug; radiopharmaceutical agent; catalysis; hydrolysis; lewis acid; chemical reaction; synthesis; radiochemistry; microwave radiation; reaction time; coupling reaction; purification; nucleosides; microwave; uracil derivative; [; 18f]-fiau; fluorine-18; 2' deoxy 2' fluoro 1 alpha,beta dextro arabinofuranosyl 5 ethyluracil; 2' deoxy 2' fluoro 1 alpha,beta dextro arabinofuranosyl 5 iodouracil; 2' deoxy 2' fluoro 1 alpha,beta dextro arabinofuranosyl 5 methyluracil; 2' fluoro 2' deoxy 3',5' di o benzoyl 1 alpha,beta dextro arabinofuranosyl 5 ethyluracil; 2' fluoro 2' deoxy 3',5' di o benzoyl 1 alpha,beta dextro arabinofuranosyl 5 iodouracil; 2' fluoro 2' deoxy 3',5' di o benzoyl 1 alpha,beta dextro arabinofuranosyl 5 methyluracil; 5 ethyl 2' fluorouracil arabinoside derivative f 18; trifluoromethanesulfonic acid; trifluoromethanesulfonic acid trimethylsilyl ester |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 39 |
| Issue: | 8 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2012-11-01 |
| Start Page: | 1182 |
| End Page: | 1188 |
| Language: | English |
| DOI: | 10.1016/j.nucmedbio.2012.06.008 |
| PROVIDER: | scopus |
| PUBMED: | 22819195 |
| PMCID: | PMC3517724 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 December 2012" - "CODEN: NMBIE" - "Source: Scopus" |
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