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

Abstract

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(δ_Ga+ 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 K_s 24.9, 298 K) which dissociates at low pH (< 2) as measured by HPLC and ¹³C NMR spectrometry.