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Fully Automated Cassette-Based Synthesis of 2-Deoxy-2-[18F]Fluorocellobiose Using Trasis AllInOne Module
Falguni Basuli1, Jianfeng Shi1, Swati Shah2
1Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, Maryland, USA.
Abstract:
Due to the continuous rise in global incidence and severity of invasive fungal infections (IFIs), particularly among immunocompromised and immunodeficient patients, there is an urgent demand for swift and accurate fungal pathogen diagnosis. Therefore, the need for fungal-specific positron emission tomography (PET) imaging agents that can detect the infection in the early stages is increasing. Cellobiose, a disaccharide, is readily metabolized by fungal pathogens such as Aspergillus species. Recently, our group reported fluorine-18 labeled cellobiose, 2-deoxy-2-[18F]fluorocellobiose ([18F]FCB), for specific imaging of Aspergillus infection. The positive imaging findings with very low background signal on delayed imaging make this ligand a promising fungal-specific imaging ligand. Inspired by this result, the decision was made to automate the radiolabeling procedure for better reproducibility and to facilitate clinical translation. A Trasis AllInOne (Trasis AIO) automated module was used for this purpose. The reagent vials contain commercially available 2-deoxy-2-[18F]fluoroglucose ([18F]FDG), glucose-1-phosphate, and enzyme (cellobiose phosphorylase). A Sep-Pak cartridge was used to purify the tracer. The overall radiochemical yield was 50%-70% (n = 6, decay corrected) in 75-min synthesis time with a radiochemical purity of > 98%. This is a highly reliable protocol to produce current good manufacturing practice (cGMP)-compliant [18F]FCB for clinical PET imaging.
Insights
Automated synthesis of 2-deoxy-2-[18F]fluorocellobiose ([18F]FCB) allows for rapid, reproducible production of this fungal-specific PET imaging agent. This method supports clinical translation for early detection of invasive fungal infections.
Area of Science:
- Nuclear medicine
- Radiochemistry
- Medical imaging
Background:
- Invasive fungal infections (IFIs) pose a growing threat, especially to immunocompromised individuals.
- Accurate and early diagnosis is crucial for effective treatment of IFIs.
- Current diagnostic methods lack specificity and speed, highlighting the need for novel imaging agents.
Purpose of the Study:
- To automate the radiolabeling of 2-deoxy-2-[18F]fluorocellobiose ([18F]FCB) for improved reproducibility and clinical translation.
- To develop a reliable method for producing current good manufacturing practice (cGMP)-compliant [18F]FCB.
- To facilitate the use of [18F]FCB as a fungal-specific positron emission tomography (PET) imaging agent.
Main Methods:
- Automated synthesis of [18F]FCB using a Trasis AllInOne module.
- Utilized commercially available 2-deoxy-2-[18F]fluoroglucose ([18F]FDG), glucose-1-phosphate, and cellobiose phosphorylase.
- Purification of the tracer using a Sep-Pak cartridge.
Main Results:
- Achieved an overall radiochemical yield of 50%-70% (decay corrected) in a 75-minute synthesis time.
- Obtained a radiochemical purity of >98% for the [18F]FCB tracer.
- Demonstrated a highly reliable and reproducible automated radiolabeling protocol.
Conclusions:
- The automated synthesis protocol provides a reliable method for producing cGMP-compliant [18F]FCB.
- This automated process is suitable for clinical translation, enabling early detection of fungal infections.
- [18F]FCB shows promise as a specific PET imaging agent for fungal pathogens.
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