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Automated Radiochemical Synthesis of [18F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases
Published on: May 29, 2017
Radiosynthesis of [18F]FPenM-C2Am: A PET Imaging Agent for Detecting Cell Death
Flaviu Bulat1, André A A Neves1, Kevin M Brindle2
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Abstract:
Imaging agents capable of detecting the extent, timing, and distribution of tumor cell death following treatment could be used in clinical trials of novel cancer therapies to get an early indication of efficacy and subsequently in the clinic to guide treatment in individual patients. We have shown how the C2A domain of synaptotagmin I, which binds the phosphatidylserine exposed by apoptotic and necrotic cells, can be used to image cell death (Bulat et al., EJNMMI Res 10(1):151, 2020; Neves et al. J Nucl Med 58(6):881-887, 2017). We describe here the semi-automated 18F labeling of the single cysteine residue in the protein (C2Am) that had been introduced by site-directed mutagenesis.
Insights
This study introduces a new method for imaging cancer cell death using a modified protein (C2Am). This technique allows for semi-automated fluorine-18 labeling, improving cancer therapy assessment.
Area of Science:
- Biochemistry
- Molecular Imaging
- Radiochemistry
Background:
- Imaging agents are crucial for assessing cancer therapy efficacy by detecting tumor cell death.
- The C2A domain of synaptotagmin I binds phosphatidylserine, a marker of cell death, enabling imaging.
- Previous work demonstrated the utility of C2A domain for cell death imaging.
Purpose of the Study:
- To describe the semi-automated 18F labeling of a C2A domain protein variant (C2Am).
- To facilitate the development of novel imaging agents for monitoring cancer treatment response.
Main Methods:
- Site-directed mutagenesis was used to introduce a single cysteine residue into the C2A domain (C2Am).
- A semi-automated protocol was developed for incorporating fluorine-18 (18F) into the C2Am protein.
- The labeled C2Am was prepared for potential use as a cell death imaging agent.
Main Results:
- Successfully achieved semi-automated 18F labeling of the C2Am protein.
- The developed method enables the preparation of a radiolabeled protein for imaging applications.
- This advances the potential for clinical use in evaluating cancer therapies.
Conclusions:
- The semi-automated 18F labeling of C2Am provides a viable method for developing cell death imaging agents.
- This technique can aid in early assessment of novel cancer therapies and personalized treatment guidance.
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