A Convenient Route to New (Radio)Fluorinated and (Radio)Iodinated Cyclic Tyrosine Analogs

The use of radiolabeled non-natural amino acids can provide high contrast SPECT/PET metabolic imaging of solid tumors. Among them, radiohalogenated tyrosine analogs (i.e., [ I]IMT, [ F]FET, [ F]FDOPA, [ I]8-iodo-L-TIC(OH), etc.) are of particular interest. While radioiodinated derivatives, such as [...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2022-01, Vol.15 (2), p.162
Main Authors: Chao, Maria Noelia, Chezal, Jean-Michel, Debiton, Eric, Canitrot, Damien, Witkowski, Tiffany, Levesque, Sophie, Degoul, Françoise, Tarrit, Sébastien, Wenzel, Barbara, Miot-Noirault, Elisabeth, Serre, Audrey, Maisonial-Besset, Aurélie
Format: Article
Language:English
Subjects:
Amino acids
Brain cancer
Fluorine
Iodine
Kinases
Life Sciences
Peptides
PET/SPECT imaging
Phosphatase
radiofluorination
radioiodination
Radioisotopes
TIC(OH)
Tomography
Tumors
tyrosine analogs
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Summary:The use of radiolabeled non-natural amino acids can provide high contrast SPECT/PET metabolic imaging of solid tumors. Among them, radiohalogenated tyrosine analogs (i.e., [ I]IMT, [ F]FET, [ F]FDOPA, [ I]8-iodo-L-TIC(OH), etc.) are of particular interest. While radioiodinated derivatives, such as [ I]IMT, are easily available via electrophilic aromatic substitutions, the production of radiofluorinated aryl tyrosine analogs was a long-standing challenge for radiochemists before the development of innovative radiofluorination processes using arylboronate, arylstannane or iodoniums salts as precursors. Surprisingly, despite these methodological advances, no radiofluorinated analogs have been reported for [ I]8-iodo-L-TIC(OH), a very promising radiotracer for SPECT imaging of prostatic tumors. This work describes a convenient synthetic pathway to obtain new radioiodinated and radiofluorinated derivatives of TIC(OH), as well as their non-radiolabeled counterparts. Using organotin compounds as key intermediates, [ I]5-iodo-L-TIC(OH), [ I]6-iodo-L-TIC(OH) and [ I]8-iodo-L-TIC(OH) were efficiently prepared with good radiochemical yield (RCY, 51-78%), high radiochemical purity (RCP, >98%), molar activity (Am, >1.5-2.9 GBq/µmol) and enantiomeric excess (e.e. >99%). The corresponding [ F]fluoro-L-TIC(OH) derivatives were also successfully obtained by radiofluorination of the organotin precursors in the presence of tetrakis(pyridine)copper(II) triflate and nucleophilic [ F]F with 19-28% RCY d.c., high RCP (>98.9%), Am (20-107 GBq/µmol) and e.e. (>99%).
ISSN:1424-8247
1424-8247
DOI:10.3390/ph15020162