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Automation of a Positron-emission Tomography (PET) Radiotracer Synthesis Protocol for Clinical Production
Published on: October 26, 2018
Novel PET probes specific for deoxycytidine kinase
Chengyi J Shu1, Dean O Campbell, Jason T Lee
1Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Summary
New PET probes, L-(18)F-FAC and L-(18)F-FMAC, show improved metabolic stability and specificity for deoxycytidine kinase (dCK). These probes can effectively image dCK activity in animal models, paving the way for human studies.
Area of Science:
- Biochemistry
- Radiochemistry
- Molecular Imaging
Background:
- Deoxycytidine kinase (dCK) is crucial for nucleoside analog prodrug efficacy.
- dCK activity is a key indicator in immune disorders and cancers.
- Previous PET probe (18)F-FAC showed potential for dCK imaging.
Purpose of the Study:
- Develop novel PET probes with enhanced metabolic stability and specificity for dCK.
- Synthesize and evaluate new candidate PET probes for dCK activity.
- Improve imaging of dCK-related conditions.
Main Methods:
- Synthesized novel L-nucleoside analogs of (18)F-FAC.
- Assessed metabolic stability using high-pressure liquid chromatography.
- Determined dCK affinity via in vitro kinase and uptake assays.
- Evaluated biodistribution in mice using small-animal PET/CT.
Main Results:
- Identified L-(18)F-FAC and L-(18)F-FMAC as promising PET probes.
- These probes exhibited low deamination susceptibility and high dCK affinity.
- Successfully imaged dCK activity in animal models of leukemia and autoimmunity.
Conclusions:
- L-(18)F-FAC and L-(18)F-FMAC demonstrate significant potential for PET imaging of dCK.
- Further biodistribution and dosimetry studies in humans are warranted.
- These probes could advance diagnostics and therapeutic monitoring for dCK-related diseases.
