[en] Induction of apoptosis is often necessary for successful cancer therapy, and the non-invasive monitoring of apoptosis post-therapy could assist in clinical decision making. Isatins are a class of compounds that target activated caspase-3 during apoptosis. Here we report the synthesis of the 5-iodo-1,2,3-triazole (FITI) analog of the PET tracer [18F]ICMT11 as a candidate tracer for imaging of apoptosis with SPECT, as well as PET. Labelling with radioiodine (123,125I) was achieved in 55 ± 12% radiochemical yield through a chelator-accelerated one-pot cycloaddition reaction mediated by copper(I) catalysis. The caspase-3 binding affinity and selectivity of FITI compares favourably to that of [18F]ICMT11 (Ki = 6.1 ± 0.9 nM and 12.4 ± 4.7 nM, respectively). In biodistribution studies, etoposide-induced cell death in a SW1222 xenograft model resulted in a 2-fold increase in tumour uptake of the tracer. However, the tumour uptake was too low to allow in vivo imaging of apoptosis with SPECT.
Disciplines :
Radiology, nuclear medicine & imaging Chemistry
Author, co-author :
Glaser, Matthias; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London, WC1E 6BS, United Kingdom ; Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, United Kingdom
Rajkumar, Vineeth; UCL, Cancer Institute, 72 Huntley Street, London, WC1E 6DD, UK
Diocou, Seckou; UCL, Cancer Institute, 72 Huntley Street, London, WC1E 6DD, UK
Gendron, Thibault ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique-nucléaire ; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London, WC1E 6BS, United Kingdom ; Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, United Kingdom
Yan, Ran; King's College London, School of Biomedical Engineering and Imaging Sciences, St. Thomas' Hospital, SE1 7EH, London, United Kingdom
Sin, Pak Kwan Brian; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London, WC1E 6BS, United Kingdom
Sander, Kerstin; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London, WC1E 6BS, United Kingdom ; Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, United Kingdom
Carroll, Laurence; Imperial College London, Science, Technology & Medicine, Department of Medicine, Hammersmith Hospital, DuCane Road, London, W12 0NN, United Kingdom
Pedley, R Barbara; UCL, Cancer Institute, 72 Huntley Street, London, WC1E 6DD, UK
Aboagye, Eric O; Imperial College London, Science, Technology & Medicine, Department of Medicine, Hammersmith Hospital, DuCane Road, London, W12 0NN, United Kingdom
Witney, Timothy H; King's College London, School of Biomedical Engineering and Imaging Sciences, St. Thomas' Hospital, SE1 7EH, London, United Kingdom ; Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, United Kingdom
Årstad, Erik ; Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London, WC1E 6BS, United Kingdom. e.arstad@ucl.ac.uk ; Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, United Kingdom. e.arstad@ucl.ac.uk
Language :
English
Title :
One-Pot Radiosynthesis and Biological Evaluation of a Caspase-3 Selective 5-[123,125I]iodo-1,2,3-triazole derived Isatin SPECT Tracer.
CRUK - Cancer Research UK [GB] Wellcome Trust [US] EPSRC - Engineering and Physical Sciences Research Council [GB]
Funding text :
The authors would like to thank Vincent Gray, Mathew Robson, and Tammy Kalber for their expert technical support. This work was supported by CRUK & EPSRC Comprehensive Cancer Imaging Centre at KCL, UCL & Imperial jointly funded by Cancer Research UK and the Engineering and Physical Sciences Research Council (EPSRC; C1519/A16463; C2536/A10337) (M.G., T.G. and L.C.), and an EPSRC Case Studentship in partnership with GE (P.K.B.S.). T.H.W. was supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 107610/Z/15/Z). This work was undertaken at UCLH/UCL, which is funded in part by the Department of Health’s NIHR Biomedical Research Centres funding scheme.
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