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Automated synthesis of (18)F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry
BACKGROUND: Oncrasin-1 is a small molecule which was identified from a screen of KRAS mutant cancer cells and has shown specificity for KRAS mutant cell killing. We aimed to develop a radiolabelled form of Oncrasin-1 to enable in-vivo imaging of mutant KRAS expression in malignant tumours. This work...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652984/ https://www.ncbi.nlm.nih.gov/pubmed/33169204 http://dx.doi.org/10.1186/s41181-020-00104-x |
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author | McDonald, Alexander F. Goh, Yit Wooi White, Jonathan M. Scott, Andrew M. Ackermann, Uwe |
author_facet | McDonald, Alexander F. Goh, Yit Wooi White, Jonathan M. Scott, Andrew M. Ackermann, Uwe |
author_sort | McDonald, Alexander F. |
collection | PubMed |
description | BACKGROUND: Oncrasin-1 is a small molecule which was identified from a screen of KRAS mutant cancer cells and has shown specificity for KRAS mutant cell killing. We aimed to develop a radiolabelled form of Oncrasin-1 to enable in-vivo imaging of mutant KRAS expression in malignant tumours. This work outlines the synthesis of 3 fluorinated derivatives and development of iodonium salt and boronic ester precursors for radiolabelling with the (18)F isotope. RESULTS: In our hands, synthesis of iodonium salts were not easily accessible due to the 3-carbaldehyde indole structure being preferentially oxidized by conditions required for iodonium salt formation, rather than benzyl iodide. Synthesis and radiolabelling of boronic acid pinacol ester precursors were successful, with the products being obtained in yields of 10.76% ± 0.96% (n = 5), 14.7% ±8.58% (n = 3) and 14.92% ±3.9% (n = 3) for (18)F KAM001, (18)F KAM002 and (18)F KAM003 respectively, with radiochemical purity of greater than 99%. CONCLUSIONS: The successful synthesis of these tracers has been undertaken utilizing boronic ester radio-fluorination methods and will allow for investigation of Oncrasin based molecules as potential diagnostics for cancers expressing mutant KRAS protein. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s41181-020-00104-x. |
format | Online Article Text |
id | pubmed-7652984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-76529842020-11-12 Automated synthesis of (18)F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry McDonald, Alexander F. Goh, Yit Wooi White, Jonathan M. Scott, Andrew M. Ackermann, Uwe EJNMMI Radiopharm Chem Research Article BACKGROUND: Oncrasin-1 is a small molecule which was identified from a screen of KRAS mutant cancer cells and has shown specificity for KRAS mutant cell killing. We aimed to develop a radiolabelled form of Oncrasin-1 to enable in-vivo imaging of mutant KRAS expression in malignant tumours. This work outlines the synthesis of 3 fluorinated derivatives and development of iodonium salt and boronic ester precursors for radiolabelling with the (18)F isotope. RESULTS: In our hands, synthesis of iodonium salts were not easily accessible due to the 3-carbaldehyde indole structure being preferentially oxidized by conditions required for iodonium salt formation, rather than benzyl iodide. Synthesis and radiolabelling of boronic acid pinacol ester precursors were successful, with the products being obtained in yields of 10.76% ± 0.96% (n = 5), 14.7% ±8.58% (n = 3) and 14.92% ±3.9% (n = 3) for (18)F KAM001, (18)F KAM002 and (18)F KAM003 respectively, with radiochemical purity of greater than 99%. CONCLUSIONS: The successful synthesis of these tracers has been undertaken utilizing boronic ester radio-fluorination methods and will allow for investigation of Oncrasin based molecules as potential diagnostics for cancers expressing mutant KRAS protein. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s41181-020-00104-x. Springer International Publishing 2020-11-09 /pmc/articles/PMC7652984/ /pubmed/33169204 http://dx.doi.org/10.1186/s41181-020-00104-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article McDonald, Alexander F. Goh, Yit Wooi White, Jonathan M. Scott, Andrew M. Ackermann, Uwe Automated synthesis of (18)F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry |
title | Automated synthesis of (18)F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry |
title_full | Automated synthesis of (18)F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry |
title_fullStr | Automated synthesis of (18)F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry |
title_full_unstemmed | Automated synthesis of (18)F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry |
title_short | Automated synthesis of (18)F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry |
title_sort | automated synthesis of (18)f radiolabelled indole containing oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652984/ https://www.ncbi.nlm.nih.gov/pubmed/33169204 http://dx.doi.org/10.1186/s41181-020-00104-x |
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