Alan D. Watson

The use of gadolinium and dysprosium chelate complexes as contrast agents for magnetic resonance imaging

Abstract Polyaminopolycarboxylic acid complexes of gadolinium are now finding widespread application as magnetic resonance contrast agents based primarily upon their ability to alter T1 and T2 relaxation rates in vivo. Both gadolinium and dysprosium complexes are also beginning to be utilized as T 2 ∗ , or magnetic susceptibility contrast agents, to image perfusion in the human heart and brain or to enhance contrast in functional and perfusion imaging applications. The ability of a lanthanide to produce this effect is related to the square of its magnetic moment; dysprosium complexes (μ10.6 BM) appear optimal for this application and are likely to have major advantages in the clinical setting. The properties of the gadolinium and dysprosium complexes that are currently, or have been, under investigation as either relaxation-based or susceptibility agents (or both) are discussed. Particular attention is paid to the ligand type, acyclic or cyclic, since this is a major determinant of the physicochemical and biological properties of these complexes. The physicochemical characterization and development of a new nonionic dysprosium complex, DyDTPA-BMA (Sprodiamide), as a heart and brain imaging agent is described.

The synthesis, characterization and biological studies of a dimeric W3S4 cluster complex: a new potential X-ray contrast agent

Abstract An EGTA complex of the incomplete cubane-type, trinuclear tungsten sulfur cluster, [W3S4], was prepared and investigated as a possible candidate for a new generation of X-ray contrast agents for medical diagnostic imaging. The aqua ion, [W3S4(H2O)9]4+ (I) was prepared through an improvement of the literature method to facilitate scale-up. Reaction of I with EGTA in refluxing DMF produced a mixture of (W3S4)x(EGTA)y (x,y ≥ 1) cluster complexes. A 2:3(W3S4:ligand) complex, [(W3S4)2(EGTA)3]4− (II), was isolated via size-exclusion chromatography in 25–40% yield. Cluster complex II was fully characterized by X-ray crystallography in addition to routine techniques. It is soluble in H2O and stable in the pH range 2 to 10. Animal studies of II indicated a low acute toxicity and a pharmacokinetic profile similar to that of an existing heavy metal cluster complex with a known extracellular biodistribution.