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Updated: Jan 1, 2026
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Published on: April 28, 2019
One-Pot Radiosynthesis and Biological Evaluation of a Caspase-3 Selective 5-[123,125I]iodo-1,2,3-triazole derived
Matthias Glaser1,2, Vineeth Rajkumar3, Seckou Diocou3
1Centre for Radiopharmaceutical Chemistry, University College London, 5 Gower Place, London, WC1E 6BS, United Kingdom.
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.
Insights
Researchers developed a new imaging agent, 5-iodo-1,2,3-triazole (FITI), to detect apoptosis, a key process in cancer therapy. While FITI shows promise in binding caspase-3, its low tumor uptake limits SPECT imaging capabilities.
Area of Science:
- Biomedical imaging
- Radiochemistry
- Molecular imaging
Background:
- Apoptosis monitoring is crucial for effective cancer therapy.
- Isatins are a class of compounds targeting activated caspase-3 during apoptosis.
- Developing non-invasive imaging tracers for apoptosis is clinically significant.
Purpose of the Study:
- To synthesize and evaluate 5-iodo-1,2,3-triazole (FITI) as a SPECT/PET imaging tracer for apoptosis.
- To assess FITI's caspase-3 binding affinity and selectivity.
- To investigate FITI's biodistribution and tumor uptake in a xenograft model.
Main Methods:
- Synthesis of FITI analog of [18F]ICMT11.
- Radiolabeling with radioiodine (123,125I) using copper(I) catalysis.
- In vitro assessment of caspase-3 binding affinity and selectivity.
- In vivo biodistribution studies in a SW1222 xenograft model.
Main Results:
- FITI was synthesized with a 55 ± 12% radiochemical yield.
- FITI demonstrated favorable caspase-3 binding affinity (Ki = 6.1 ± 0.9 nM) compared to [18F]ICMT11.
- Etoposide treatment increased tumor uptake of FITI by 2-fold, but overall uptake was insufficient for SPECT imaging.
Conclusions:
- FITI is a potential apoptosis imaging agent with good caspase-3 binding.
- The low tumor uptake of FITI currently limits its utility for in vivo SPECT imaging of apoptosis.
- Further optimization may be needed to enhance tumor targeting and imaging performance.
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