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 In-111, triazacyclononanetraicetate bound indium most quickly and formed a complex whose dissociation as a function of pD was monitored by C-13 NMR spectrometry using a labelled ligand (k296 1.8 x 10(-4) 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 Ga-71 NMR spectrometry both in vitro (delta-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 Y-90 reported. Ligands based on tetraazacyclododecane bind Y-90 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 C-13 NMR spectrometry.