Abstract
Isatin-5-sulfonamide ([(18)F]ICMT-11) is a sub-nanomolar inhibitor of caspase-3 previously evaluated as an apoptosis imaging agent. Herein, an alternative radiosynthesis of [(18)F]ICMT-11 with increased purity and specific activity is presented. Finally, a GMP-applicable automated radiosynthesis of [(18)F]ICMT-11 is described. The preparation of [(18)F]ICMT-11 was evaluated under a variety of reaction conditions, including reaction solvent, by employing alternative phase transfer catalysts and under different deprotection conditions. Following initial investigations, the process was transferred onto a fully automated GE FASTlab synthesis platform for further development and optimisation. The synthesis of [(18)F]ICMT-11 was successfully validated under GMP conditions, resulting in a yield of 4.6 ± 0.4 GBq with a radiochemical purity of >98% at EOS and a specific activity of 685 ± 237 GBq/μmol within 90 min. Quality control was carried out in accordance with the European Pharmacopoeia and demonstrated that [(18)F]ICMT-11 can be consistently manufactured on the FASTlab to meet specifications. A simplified methodology for the synthesis of the apoptosis imaging agent, [(18)F]ICMT-11, has been achieved by the S(N)2 displacement of a ...Continue Reading
References
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Jun 29, 2000·Annual Review of Biochemistry·W C EarnshawS H Kaufmann
Dec 12, 2001·Organic Letters·Z P Demko, K B Sharpless
Jul 18, 2002·Nature Reviews. Drug Discovery·Jason Y Zhang
Nov 24, 2005·Journal of Medicinal Chemistry·Wenhua ChuRobert H Mach
Dec 13, 2006·Journal of Medicinal Chemistry·Klaus KopkaBodo Levkau
Jul 17, 2008·Bioconjugate Chemistry·Xuehe LiJonathan F Tait
Dec 4, 2008·Journal of Medicinal Chemistry·Graham SmithEric O Aboagye
Mar 21, 2009·Organic & Biomolecular Chemistry·Dong ZhouRobert H Mach
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Mar 29, 2011·Bioorganic & Medicinal Chemistry Letters·Wenhua ChuRobert H Mach
Oct 28, 2011·Bioorganic & Medicinal Chemistry Letters·Matthias GlaserEric O Aboagye
Citations
Mar 13, 2014·PloS One·Timothy H WitneyEric O Aboagye
Jul 25, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marc PretzeConstantin Mamat
Jul 2, 2015·Future Medicinal Chemistry·Panupun LimpachayapornGünter Haufe
Jul 9, 2014·BioMed Research International·Kathrin KettenbachTobias L Ross
Jun 14, 2017·Chemical Society Reviews·Dion van der BornDanielle J Vugts
Mar 13, 2017·Bioorganic & Medicinal Chemistry·Christian Paul OrtmeyerVerena Hugenberg
Apr 14, 2015·Organic & Biomolecular Chemistry·A UdembaE O Aboagye
Mar 13, 2018·Medicinal Research Reviews·Anna A RybczynskaAren van Waarde
Jan 22, 2017·Oncotarget·Xiaobo WangWenbin Zeng
Apr 8, 2020·Cancers·Louis AllottEric O Aboagye
Feb 21, 2019·EJNMMI Research·Vessela VassilevaEric O Aboagye
Dec 19, 2019·Scientific Reports·Matthias GlaserErik Årstad
Aug 13, 2020·Cancers·Segundo Francisco García-ArgüelloGraham Smith
Apr 2, 2020·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Alvaro A OrdonezSanjay K Jain
Sep 28, 2018·European Journal of Nuclear Medicine and Molecular Imaging·S R DubashEric O Aboagye
Jun 5, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Quang-Dé NguyenEric O Aboagye
Jan 28, 2020·Journal of Labelled Compounds & Radiopharmaceuticals·Imtiaz KhanWilliam Trigg
May 1, 2021·International Journal of Molecular Sciences·Lucas BeroskeFilipe Elvas
May 26, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Kathrin HeinzmannEric Aboagye
Aug 21, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Amarnath ChallapalliEric O Aboagye
May 21, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Richard EdwardsTimothy H Witney
Feb 6, 2017·Bioconjugate Chemistry·Federica PisaneschiSteven W Millward
May 10, 2013·Journal of Medicinal Chemistry·Panupun LimpachayapornGünter Haufe
May 21, 2020·Molecular Pharmaceutics·Louis Allott, Eric O Aboagye