Scott M. Rocklage

The relationship between thermodynamics and the toxicity of gadolinium complexes

The suitability of gadolinium complexes as magnetic resonance imaging contrast agents depends on a number of factors. A thermodynamic relationship to toxicity exists if one assumes that the chemotoxicity of the intact complex is minimal but that the toxicity of the components of the complex (free metal and uncomplexed ligands) is substantial. Release of Gd3+ from the complex is responsible for the toxicity associated with gadolinium complexes; this release appears to be a consequence of Zn2+, Cu2+, and Ca2+ transmetallation in vivo. This hypothesis is supported by acute toxicity experiments, which demonstrate that despite a 50-fold range of LD50 values for four Gd complexes, all become lethally toxic when they release precisely the same quantity of Gd3+, and by subchronic rodent toxicity experiments, which demonstrate a set of gross and microscopic findings similar to those known to be caused by Zn2+ deficiency. Finally, this hypothesis predicts that subtle changes in formulation can further enhance the intrinsic safety of these complexes.

Amyloidosis and alzheimer's disease diagnostic assay and reagents therefor

The presence and location of amyloid deposits in an organ or body area of a patient is effected by intravenous administration of novel radioactive iodine-labeled amyloid binding compounds and preferably 123 I-labeled compounds to the patient and sensing radiation emitted from the organ or body area. Novel non-radioactive iodine substituted amyloid binding compounds and amyloid binding compounds which are readily iodinated are further aspects of the invention.

Composition of a n-carboxymethylated tetraazacyclododecane chelating agent, a paramagnetic metal and excess calcium ions for MRI

Magnetic resonance imaging contrast media used to affect the relaxation times of atoms in body tissues undergoing NMR diagnosis are disclosed. Such media comprise (1) a paramagnetic, physiologically compatible complex of (a) a chelant consisting of a N-carboxy methylated tetraazacyclododecane, and (b) a paramagnetic ion of a lanthanide element of atomic numbers 59-70, or of a transition metal of atomic numbers 21-29, 42 or 44, or a physiologically compatible salt of such a complex, and (2) a toxicity-reducing amount of labile calcium ions. The labile calcium ions can be derived from a source other than a salt of said chelant, e.g. an inorganic or organic calcium salt. NMR image-enhancing compositions comprising NMR image-enhancing effective amounts of said contrast media and pharmaceutically acceptable diluents are also disclosed.

5039512 NMR imaging with paramagnetic polyvalent metal salts of poly-(acid-alkylene-amino) -alkanes

In a method of imaging body tissue in a patient, comprising administering to the patient an effective amount of a pharmaceutical agent for effecting the relaxation times of atoms in body tissues undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to effect such relaxation times, of a paramagnetic, physiologically compatible salt of a physiologically compatible chelate complex of an ion of a lanthanide element of atomic numbers 57-70, or of a transition metal of atomic numbers 21-29, 42, or 44; and a pharmaceutically acceptable carrier, and subjecting the patient to NMR tomography, the improvement wherein said salt of said chelate complex is the calcium or magnesium salt. Such salts are new as are some of the complexing chelates.