Organic compounds -- part of the class 532-570 series – Organic compounds – Radioactive metal containing
Patent
1996-02-08
1998-08-04
Kight, John
Organic compounds -- part of the class 532-570 series
Organic compounds
Radioactive metal containing
534 10, 424 111, 424 165, C07F 1300
Patent
active
057895554
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to compositions and processes useful for generating metal-ligand complexes. In one specific respect, the invention relates to metal-labelled compounds useful as imaging agents in the field of medical diagnostics.
BACKGROUND OF THE INVENTION
The art of diagnostic imaging exploits agents that in binding or localizing site selectively within the body, help to resolve the image of diagnostic interest. Gallium citrate, for example, has an affinity for tumours and infected tissue of the body and, with the aid of scanning tomography, can reveal afflicted body regions to a physician. Magnetic Resonance Imaging (MRI) differentiates tissue types by their physicochemical properties and can therefore detect tissues altered physicochemically by disease. To enhance detection, imaging agents are employed that affect the rate of proton relaxation of water molecules in the body upon irradiation by a magnetic field. Typical MRI agents comprise a water soluble, non-toxic organic chelator complexed with a paramagnetic metal, for example gadolinium-ethylenediaminetetraacetic acid (Gd-EDTA). Other imaging agents used in diagnostic imaging incorporate targeting molecules, such as proteins, peptides and antibodies that localize at desired regions of the human body and are labelled with a radionuclide metal such as technetium and rhenium. Localization of these imaging agents is detected by gamma camera analysis.
Labelling of imaging agents with metal atoms is made difficult by their chemical structure. Conventional labelling techniques involve the formation of the metal complex in a solution of excess ligand which typically results in high levels of unlabelled ligand. For example, technetium labelling reactions yield approximately one labelled ligand for every thousand or more unlabelled ligand. For many imaging agents, there is a finite number of binding sites ie. receptors, for which both the labelled and unlabelled imaging agent compete. This necessitates administration of larger doses of the imaging agent in order to achieve an image. Presently, high performance liquid chromatography (HPLC) is applied to enhance the concentration of labelled imaging agent in the solution before it is administered. While enhancing concentration, this separation step requires additional time and expense which make it impractical for clinical use.
It is an object of the present invention to provide a composition useful for generating labelled imaging agent.
It is also an object of the present invention to provide a process for preparing compositions useful for generating labelled imaging agent that is substantially free of unlabelled imaging agent.
A further object of the present invention is to provide a method of using compositions to generate preparations of labelled imaging agent that are substantially free of unlabelled imaging agent, in particular metal-labelled compounds useful for diagnostic imaging.
SUMMARY OF THE INVENTION
According to one aspect of the invention, there is provided a composition useful for generating a metal labelled imaging agent comprising: a solid support; a linking group bound to the solid support; and a ligand incorporating at least one metal coordinating atom that is coupled to the linking group by a bond cleavable by said metal wherein said ligand is further coupled to a targeting molecule that is free of metal binding sites.
According to another aspect of the present invention, there is provided a process for generating a metal-ligand complex, comprising the steps of is coupled to a linking group bound to a solid support wherein the ligand is further coupled to a targeting molecule thereby forming a ligand-targeting molecule conjugate; formation of a coordinate bond between the metal and the metal coordinating atom and thereby to cause release of a metal labelled conjugate from the support; and
In a further aspect of the invention, there is provided a composition useful for generating a metal labelled imaging agent, the composition comprising: a solid support;
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Jones Dameron
Kight John
Resolution Pharmaceuticals Inc.
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