One-Pot Radiosynthesis and Biological Evaluation of a Caspase-3 Selective 5-[123,125I]iodo-1,2,3-triazole derived Isatin SPECT Tracer

Matthias Glaser, Vineeth Rajkumar, Seckou Diocou, Thibault Gendron, Ran Yan, Pak Kwan Brian Sin, Kerstin Sander, Laurence Carroll, R. Barbara Pedley, Eric O. Aboagye, Timothy H. Witney, Erik Årstad

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number19299
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Isatin
Triazoles
Single-Photon Emission-Computed Tomography
Caspase 3
Apoptosis
Neoplasms
Cycloaddition Reaction
Etoposide
Chelating Agents
Catalysis
Heterografts
Copper
Cell Death
Therapeutics

ASJC Scopus subject areas

  • General

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One-Pot Radiosynthesis and Biological Evaluation of a Caspase-3 Selective 5-[123,125I]iodo-1,2,3-triazole derived Isatin SPECT Tracer. / Glaser, Matthias; Rajkumar, Vineeth; Diocou, Seckou; Gendron, Thibault; Yan, Ran; Sin, Pak Kwan Brian; Sander, Kerstin; Carroll, Laurence; Pedley, R. Barbara; Aboagye, Eric O.; Witney, Timothy H.; Årstad, Erik.

In: Scientific reports, Vol. 9, No. 1, 19299, 01.12.2019.

Research output: Contribution to journalArticle

Glaser, M, Rajkumar, V, Diocou, S, Gendron, T, Yan, R, Sin, PKB, Sander, K, Carroll, L, Pedley, RB, Aboagye, EO, Witney, TH & Årstad, E 2019, 'One-Pot Radiosynthesis and Biological Evaluation of a Caspase-3 Selective 5-[123,125I]iodo-1,2,3-triazole derived Isatin SPECT Tracer', Scientific reports, vol. 9, no. 1, 19299. https://doi.org/10.1038/s41598-019-55992-0
Glaser, Matthias ; Rajkumar, Vineeth ; Diocou, Seckou ; Gendron, Thibault ; Yan, Ran ; Sin, Pak Kwan Brian ; Sander, Kerstin ; Carroll, Laurence ; Pedley, R. Barbara ; Aboagye, Eric O. ; Witney, Timothy H. ; Årstad, Erik. / One-Pot Radiosynthesis and Biological Evaluation of a Caspase-3 Selective 5-[123,125I]iodo-1,2,3-triazole derived Isatin SPECT Tracer. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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