First in human study of 18F-FDOPA generated by photoredox radiofluorination

Introduction: Catalytic photoredox reactions continue to expand at a rapid pace and have gained tremendous interest and utility over the past several decades. Many scientific disciplines have applied photoredox strategies, including new reaction development, natural product synthesis, drug discovery, and radiolabeling. Our group has focused on photoredox radio labeling for several years, and developed various light-induced ¹⁸F-/¹¹C-labeling methods. Although these methods have been successfully used to develop PET agents, their application is mainly limited to preclinical evaluations. Due to the high demand for PET agent ¹⁸F-FDOPA, here, we report the first in human study using photoredox-generated ¹⁸F-FDOPA.

Methods: The photoredox labeling of L-¹⁸F-FDOPA was carried out by integrating the light reactor (Model PR486-450, provided by LED Radiofluidics Corp.) with the ¹⁸F-labeling module PET-MF-2V-IT-I. The labeling condition on the module was screened and the quality controls of the final product include endotoxic and residue solvent test, radio chemical yield (RCY), radiochemical purity (RCP), MCA, stability, half-life, residue catalyst test etc. The photoredox produced L-¹⁸F-FDOPA was then studied in a female schizoid patient with Parkinson's syndrome after regulatory approval.

Results: Precursor A was ¹⁸F-labeled through photoredox-mediated isotope exchange with LED lights (lightbox model PR486-450) to give the L-¹⁸F-FDOPA in with 27.7% decay corrected RCY after cartridge purification. Residue solvents and other QC measurements pass meet the traditional cGMP production of PET agents. As the new factor for photoredox labeling is the use of photocatalyst, we also evaluated the residue catalyst in the final product, which was found to be below the detection level of HPLC analysis. After ensuring the agent met the required specifications, the ¹⁸F-FDOPA generated by this method was then tested on a Parkinson's syndrome patient which showed desired imaging pattern with no adverse side effects.

Conclusions: We report the preparation of clinical grade L-¹⁸F-FDOPA by photoredox-reaction, which was then tested in patients with Parkinson's syndrome. The L-¹⁸F-FDOPA PET/CT imaging results were in good agreement with the clinical diagnosis. Demonstrating the first example of clinical use of PET agent generated by photoredox reaction is crucial as it removes barriers/concerns for future application of other PET agents generated by this method.

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