Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry

Abstract 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. T...

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Main Authors: Alexander F. McDonald, Yit Wooi Goh, Jonathan M. White, Andrew M. Scott, Uwe Ackermann
Format: Article
Language:English
Published: SpringerOpen 2020-11-01
Series:EJNMMI Radiopharmacy and Chemistry
Subjects:
Online Access:http://link.springer.com/article/10.1186/s41181-020-00104-x
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author Alexander F. McDonald
Yit Wooi Goh
Jonathan M. White
Andrew M. Scott
Uwe Ackermann
author_facet Alexander F. McDonald
Yit Wooi Goh
Jonathan M. White
Andrew M. Scott
Uwe Ackermann
author_sort Alexander F. McDonald
collection DOAJ
description Abstract 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 18F 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 18F KAM001, 18F KAM002 and 18F 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.
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spelling doaj.art-04b4395c3b2146e187c0abaf413b4ac32022-12-21T18:18:55ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2020-11-015111610.1186/s41181-020-00104-xAutomated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistryAlexander F. McDonald0Yit Wooi GohJonathan M. White1Andrew M. Scott2Uwe Ackermann3The Olivia Newton-John Cancer Research Insititute, and School of Cancer Medicine, La Trobe UniversitySchool of Chemistry, Bio21 Institute, The University of MelbourneThe Olivia Newton-John Cancer Research Insititute, and School of Cancer Medicine, La Trobe UniversityThe Olivia Newton-John Cancer Research Insititute, and School of Cancer Medicine, La Trobe UniversityAbstract 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 18F 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 18F KAM001, 18F KAM002 and 18F 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.http://link.springer.com/article/10.1186/s41181-020-00104-xRadiofluorination18F fluorinationAutomated synthesisOncologyTracer developmentIodonium salt
spellingShingle Alexander F. McDonald
Yit Wooi Goh
Jonathan M. White
Andrew M. Scott
Uwe Ackermann
Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry
EJNMMI Radiopharmacy and Chemistry
Radiofluorination
18F fluorination
Automated synthesis
Oncology
Tracer development
Iodonium salt
title Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry
title_full Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry
title_fullStr Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry
title_full_unstemmed Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry
title_short Automated synthesis of 18F radiolabelled indole containing Oncrasin-like molecules; a comparison of iodonium salts and boronic ester chemistry
title_sort automated synthesis of 18f radiolabelled indole containing oncrasin like molecules a comparison of iodonium salts and boronic ester chemistry
topic Radiofluorination
18F fluorination
Automated synthesis
Oncology
Tracer development
Iodonium salt
url http://link.springer.com/article/10.1186/s41181-020-00104-x
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