Sydnone-based prosthetic groups for radioiodination.

The potential of Strained-Promoted Sydnone-Alkyne Cycloaddition (SPSAC) for radioiodination was evaluated with model cyclooctyne-conjugated peptides. Starting with a series of sydnones with varying N3 and C4 substitution, a preliminary kinetic study with non-radioactive iodinated compounds highlighted the superiority of an arylsydnone substituted by a chlorine atom in C4 position. Interestingly, reaction rate up to 11 times higher than using an azide was achieved with the best system. Access to 125 I-labelled sydnones was granted with high efficiency from arylboronic acid precursors by copper catalyzed nucleophilic substitution. Application of SPSAC on the model peptide in radiotracer conditions showed the same trend than in non-radioactive kinetic study and complete reactions could be achieved within less than an hour for the best systems. These results are favorable for use in the production of radiopharmaceuticals with heavy halogens and increase the diversity of available bioorthogonal reaction for nuclear imaging and therapy.