Synthesis of perfluorinated analogs of DOTA and NOTA: bifunctional chelating groups with potential applications in hybrid molecular imaging

The synthesis of novel NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelating groups bearing perfluorinated appendages is described. DOTA and NOTA groups are used in the production of radiopharmaceutical agents for PET and SPECT imaging (by chelation of radioactive metal ions), as well as MRI contrast agents (by chelation of lanthanide Ln3+ ions). The novel perfluorinated variants disclosed herein will enhance the synthesis and purification of such agents, as they are compatible with fluorous purification strategies. Moreover, the perfluorous tag is anticipated to be detectable by 19F-MRI, suggesting future applications in hybrid molecular imaging such as PET–MRI.