A gallium complex with a new tripodal tris-hydroxypyridinone for potential nuclear diagnostic imaging: solution and in vivo studies of 67Ga-labeled species

The gallium(III) complex of a new tripodal 3-hydroxy-4-pyridinone (3,4-HP) chelator has been studied in terms of its physico-chemical and in vivo properties aimed at potential application as probe for nuclear imaging. In particular, based on spectrophotometric titrations, the hexa-coordinated (1:1) gallium complex appeared as the major species in a wide physiological acid-neutral pH range and its high stability (pGa = 27.5) should avoid drug-induced toxicity resulting from Ga(III) accumulation in tissues due to processes of transmetallation with endogenenous ligands or demetallation. A multinuclear (1H and 71Ga) NMR study gave some insights into the structure and dynamics of the gallium(III) chelate in solution, which are consistent with the tris-(3,4-HP) coordination and an eventual pseudo-octahedral geometry. Biodistribution and scintigraphic studies of the 67Ga(III) labelled chelate, performed in Wistar rats, confirmed the in vivo stability of the radiolabelled complex, its non interaction with blood proteins and its quick renal clearance. These results indicate good perspectives for potential application of extrafunctionalized analogues in radiodiagnostic techniques.

Grahical AbstractThe gallium(III) complex of a new tripodal 3-hydroxy-4-pyridinone (3,4-HP) chelator has been studied in solution in terms of its physico–chemical and in vivo properties, such as stability, biodistribution and scintigraphic studies of the 67Ga(III) labelled chelate in Wistar rats, aimed at potential application as probe for nuclear imaging.Figure optionsDownload as PowerPoint slide