The present invention provides contrast agents of the formula [N(A.sub.1,A.sub.2,A.sub.3) M](counter ion(s)) for use in a diagnostic method practiced on the human or animal body. It also refers to the contrast agents, as well as pharmaceutical compositions containing same. Further, it relates to a method of in vitro medical imaging, especially of diagnostic imaging, comprising administering said compound to a sample.

In some aspects, the present disclosure provides compounds of the formula:

##STR00001##

wherein the variables are defined herein. In some aspects, the present disclosure provides methods of preparing imaging agents, compositions thereof, and methods of imaging using said imaging agents or compositions thereof.

The present invention relates to a process for the preparation of a solid form of the gadobenate dimeglumine compound that comprises obtaining a solution of the said compound in a suitable solvent A wherein the amount by weight of the water optionally present in the solution is at most equal to or lower than the amount by weight of the gadobenate dimeglumine comprised in the solution and adding the obtained solution to an organic solvent B, acting as an appropriate antisolvent and favoring the formation of a solid form of the gadobenate dimeglumine that can be collected by filtration.

Disclosed herein are complexes of gadolinium metal, ligand and meglumine that are substantially free of non-aqueous solvents. In particular, solvent-free complexes of 1) gadopentetate dimeglumine and 2) gadoterate meglumine are disclosed and methods of their preparation are disclosed. In addition, methods are disclosed for purifying reactants, monitoring and controlling pH, quantifying the free gadolinium content, quantifying the concentration of gadolinium-ligand complex in aqueous solution, and procedures for producing a drug product in one step. The one step process eliminates the need to dry the gadolinium-ligand complex, which is typically highly hygroscopic. The one step process includes purification steps that do not require the use of non-aqueous solvents.

The present invention provides a method of administering a therapeutic agent directly to the brain parenchym through a compromised region of the blood-brain barrier in a subject having a brain disorder, that involves first disrupting the blood-brain barrier (BBB) at an isolated region by locally administering an effective amount of a hyperosmolar agent at said region using a catheter, followed by administering a therapeutically effective amount of a therapeutic agent. The step of disrupting the BBB is carried out with non-invasive MR (magnetic resonance) imaging with a contrast agent to visualize local parenchymal transcatheter perfusion at said isolated BBB region thereby indicating that the BBB region is compromised. The method of the invention allows for highly precise drug delivery to the brain through blood brain barrier disruption at specifically controlled regions.

Tracer kinetic models are utilized as temporal constraints for highly under-sampled reconstruction of DCE-MRI data. In one embodiment, a method for improving dynamic contrast enhanced imaging. The method includes steps of administering a magnetic resonance contrast agent to a subject and then collecting magnetic resonance contrast agent from the subject. A tracer kinetic model (i.e. eTofts or Patlak) is selected to be applied to the magnetic resonance imaging data. The tracer kinetic model is applied to the magnetic resonance imaging data. Tracer kinetic maps and dynamic images are simultaneously reconstructed and a consistency constraint is applied. The proposed method allows for easy use of different tracer kinetic models in the formulation and estimation of patient-specific arterial input functions jointly with tracer kinetic maps.

Disclosed are a multi-modality molecular imaging probe, and a preparation method and use thereof. The multi-modality molecular imaging probe has an ABA structure, with a magnetic functional unit of a gadolinium complex at the center, and two identical phosphorescent functional units of an iridium complex, which are reasonably integrated into the same one complex molecule. The multi-modality molecular imaging probe simultaneously introduces two optical functional units of the iridium complex and one magnetic functional unit of a gadolinium chelate in the same one complex molecule, which exhibits magnetic-optical dual functional properties. It therefore could be used to prepare both a contrast agent for magnetic resonance imaging and an optical probe for optical imaging.

Disclosed herein is a method for multimodal imaging during a medical procedure using magnetic resonance imaging (MRI) and Raman optical imaging which involves administering an MRI imaging contrast agent that a chemical structure having charge-transfer electronic transitions. The tissue is imaged using and MRI device and the tissue is illuminated with excitation light that has spectral components that are approximately tuned close to one of the charge-transfer electronic transitions thereby producing enhanced Raman optical signals which are analyzed to produce Raman imaging data followed by registering the MRI and Raman imaging data. The present disclosure also provides a method for ionizing laser plumes through atmospheric pressure chemical ionization.

Disclosed herein are complexes of gadolinium metal, ligand and meglumine that are substantially free of non-aqueous solvents. In particular, solvent-free complexes of 1) gadopentetate dimeglumine and 2) gadoterate meglumine are disclosed and methods of their preparation are disclosed. In addition, methods are disclosed for purifying reactants, monitoring and controlling pH, quantifying the free gadolinium content, quantifying the concentration of gadolinium-ligand complex in aqueous solution, and procedures for producing a drug product in one step. The one step process eliminates the need to dry the gadolinium-ligand complex, which is typically highly hygroscopic. The one step process includes purification steps that do not require the use of non-aqueous solvents.

Tracer kinetic models are utilized as temporal constraints for highly under-sampled reconstruction of DCE-MRI data. In one embodiment, a method for improving dynamic contrast enhanced imaging. The method includes steps of administering a magnetic resonance contrast agent to a subject and then collecting magnetic resonance contrast agent from the subject. A tracer kinetic model (i.e. eTofts or Patlak) is selected to be applied to the magnetic resonance imaging data. The tracer kinetic model is applied to the magnetic resonance imaging data. Tracer kinetic maps and dynamic images are simultaneously reconstructed and a consistency constraint is applied. The proposed method allows for easy use of different tracer kinetic models in the formulation and estimation of patient-specific arterial input functions jointly with tracer kinetic maps.