A convenient route to new (radio)fluorinated and (radio)iodinated cyclic tyrosine analogues.

The use of radiolabelled non-natural amino acids can provide high contrast SPECT/PET meta-bolic imaging of solid tumours. Among them, radiohalogenated tyrosine analogues (i.e. [123I]IMT, [18F]FET, [18F]FDOPA, [123I]8-iodo-L-TIC(OH), etc.) are of particular interest. While ra-dioiodinated derivatives, like [123I]IMT, are easily available via electrophilic aromatic substitu-tions, the production of radiofluorinated aryl tyrosine analogues was a long standing challenge for radiochemists before the development of innovative radiofluorination processes using ar-ylboronate, arylstannane or iodoniums salts as precursors. Surprisingly, despite these method-ological advances, no radiofluorinated analogues have been reported for [123I]8-iodo-L-TIC(OH), a very promising radiotracer for SPECT imaging of prostatic tumours. This work describes a convergent synthetic pathway to obtain new radioiodinated and radiofluorinated derivatives of TIC(OH), as well as their non-radiolabelled counterparts. Using organotin compounds as key intermediates, [125I]5-iodo-L-TIC(OH), [125I]6-iodo-L-TIC(OH) and [125I]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 [18F]fluoro-L-TIC(OH) derivatives were also successfully obtained by radiofluor-ination of the organotin precursors in the presence of tetrakis(pyridine)copper(II) triflate and nucleophilic [18F]F- with 19-28 % RCY d.c., high RCP (> 98.9%), Am (20-107 GBq/µmol) and e.e. (> 99%)