Orthogonal synthesis of a heterodimeric ligand for the development of the Gd^III-Ga^III ditopic complex as a potential pH-sensitive MRI/PET probe

A heterodimeric polyaminocarboxylate ligand based on a DO3A-sulfonamide linked to AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetracarboxylic acid) was synthesised via an orthogonal pathway in order to differentiate the two chelating cages and allow the formation of a Gd^III-Ga^III heteroditopic complex. The goal is to create a smart MRI/PET probe with pH dependent relaxivity and with the bimodal imaging approach that enables direct quantification of the stimulus, in this case pH. A ¹H NMR relaxometric study of the Gd-Ga heteroditopic complex addressed the pH modulation of the relaxivity and thus its possible use as an MRI pH sensitive probe.