Structure and solution stability of indium and gallium complexes of 1,4,7-triazacyclononanetriacetate and of yttrium complexes of 1,4,7,10-tetraazacyclododecanetetraacetate and related ligands: kinetically stable complexes for use in imaging and radioimmunotherapy. X-Ray molecular structure of the indium and gallium complexes of 1,4,7-triazacyclononane-1,4,7-triacetic acid

Of the four triazacycloalkanetriacetic acids screened for their ability to bind 111ln, triazacyclononanetriacetate bound indium most quickly and formed a complex whose dissociation as a function of pD was monitored by 13C NMR spectrometry using a labelled ligand (k296 1.8 × 10–1 dm3 mol–1 s–1) in the pD range 0 to –0.6. The corresponding gallium complex is even more stable with respect to acid dissociation and may be observed by 71Ga NMR spectrometry both in vitro(δGa+ 171 ppm) and in vivo. Crystal structures of the neutral gallium and of the protonated indium complexes are reported. The syntheses of a series of octadentate ligands are described and their relative efficiency to bind 90Y reported. Ligands based on tetraazacyclododecane bind 90Y most rapidly, and tetraazacyclododecanetetraacetate forms a strong complex with yttrium (log Ks 24.9, 298 K) which dissociates at low pH (< 2) as measured by HPLC and 13C NMR spectrometry.