1 research outputs found
Automated, Resin-Based Method to Enhance the Specific Activity of Fluorine-18 Clicked PET Radiotracers
Radiolabeling
of substrates with 2-[<sup>18</sup>F]Âfluoroethylazide
exploits the rapid kinetics, chemical selectivity, and mild conditions
of the copper-catalyzed azide–alkyne cycloaddition reaction.
While this methodology has proven to result in near-quantitative labeling
of alkyne-tagged precursors, the relatively small size of the fluoroethylazide
group makes separation of the <sup>18</sup>F-labeled radiotracer and
the unreacted precursor challenging, particularly with precursors
>500 Da (e.g., peptides). We have developed an inexpensive azide-functionalized
resin to rapidly remove unreacted alkyne precursor following the fluoroethylazide
labeling reaction and integrated it into a fully automated radiosynthesis
platform. We have carried out 2-[<sup>18</sup>F]Âfluoroethylazide labeling
of four different alkynes ranging from <300 Da to >1700 Da and
found that >98% of the unreacted alkyne was removed in less than
20
min at room temperature to afford the final radiotracers at >99%
radiochemical
purity with specific activities up to >200 GBq/μmol. We have
applied this technique to label a novel cyclic peptide previously
evolved to bind the Her2 receptor with high affinity, and demonstrated
tumor-specific uptake and low nonspecific background by PET/CT. This
resin-based methodology is automated, rapid, mild, and general allowing
peptide-based fluorine-18 radiotracers to be obtained with clinically
relevant specific activities without chromatographic separation and
with only a minimal increase in total synthesis time