Provided herein are magnetic resonance imaging (MRI) contrast agents comprising a compound having a structure represented by: Y—X—Z, wherein, X is: Fe(III) or Mn(II), and Y and Z are each independently selected from pyrophosphate and bisphosphonate (e.g., 1-hydroxybisphosphonate), or a pharmaceutically acceptable hydrate and/or salt thereof. Methods of use of the MRI contrast agent are also provided.

The present invention relates to compounds that are useful as metal ligands and which either contain a molecular recognition moiety or can be bound to a molecular recognition moiety and methods of making these compounds. Once the compounds that contain a molecular recognition moiety are coordinated with a suitable metallic radionuclide, the coordinated compounds are useful as radiopharmaceuticals in the areas of radiotherapy and diagnostic imaging. The invention therefore also relates to methods of diagnosis and therapy utilising the radiolabelled compounds of the invention.

Xenon based biosensors have the potential to detect and localize biomarkers associated with a wide variety of diseases. The development and nuclear magnetic resonance (NMR) characterization of cage molecules which encapsulate hyperpolarized xenon is imperative for the development of these xenon biosensors. We acquired .sup.129Xe NMR spectra, and magnetic resonance images and a HyperCEST saturation map of cucurbituril (CB6) in whole bovine blood. We observed a mean HyperCEST depletion of 84% (n=5) at a concentration of 5 mM and 74% at 2.5 mM. Additionally, we collected these data using a pulsed HyperCEST saturation pre-pulse train with a SAR of 0.025 W/kg which will minimize any potential RF heating in animal or human tissue.

Xenon based biosensors have the potential to detect and localize biomarkers associated with a wide variety of diseases. The development and nuclear magnetic resonance (NMR) characterization of cage molecules which encapsulate hyperpolarized xenon is imperative for the development of these xenon biosensors. We acquired .sup.129Xe NMR spectra, and magnetic resonance images and a HyperCEST saturation map of cucurbituril (CB6) in whole bovine blood. We observed a mean HyperCEST depletion of 84% (n=5) at a concentration of 5 mM and 74% at 2.5 mM. Additionally, we collected these data using a pulsed HyperCEST saturation pre-pulse train with a SAR of 0.025 W/kg which will minimize any potential RF heating in animal or human tissue.

Systems and methods for generating hyperpolarized target materials are disclosed. The disclosed systems and methods can include hyperpolarizing a compound then transferring polarization to a target material. The compound can be selected to have nuclear spins. The compound can be further selected to have electron spins that, when exposed to certain electromagnetic radiation, exceed a predetermined level of polarization. The compound can be exposed to such electromagnetic radiation, optically hyperpolarizing the electron spins of the compound. Polarization can then be transferred from the electron spins of the compound to nuclear spins of the compound, at least in part by exposing the compound to a magnetic field. The compound can be exposed to the target material before or after pulverizing the compound to increase the surface area of the compound, thereby facilitating transfer of polarization from the compound to the target material.

Methods for the diagnosis and treatment of ischemic spinal conditions, degenerative disc disease, back pain and/or other tissue pathologies. Patients with ischemic spine disease can be categorized into subsets that are deemed to have potential to respond to therapy. In particular, therapies are disclosed which involve stimulation of neovascularization so as to increase perfusion of spinal and other anatomies.

Methods for the diagnosis and treatment of ischemic spinal conditions, degenerative disc disease, back pain and/or other tissue pathologies. Patients with ischemic spine disease can be categorized into subsets that are deemed to have potential to respond to therapy. In particular, therapies are disclosed which involve stimulation of neovascularization so as to increase perfusion of spinal and other anatomies.

A sterile aqueous composition suitable for use as an MRI contrast agent includes 100 to 600 mM ascorbate; and 100-600 mM sodium, meglumine, or a combination thereof. The composition preferably has an osmolarity of 200 to 1400 mOsm/L.

A sterile aqueous composition suitable for use as an MRI contrast agent includes 100 to 600 mM ascorbate; and 100-600 mM sodium, meglumine, or a combination thereof. The composition preferably has an osmolarity of 200 to 1400 mOsm/L.

There is described a method for the preparation of a hyperpolarised agent, wherein said agent comprises at least one —N.sup.−, —O.sup.− or —S.sup.− moiety (optionally protonated) and a secondary binding site; said method comprising: (i) preparing a fluid containing a polarisation transfer precatalyst and parahydrogen; (ii) introducing a co-ligand to interact with the transfer precatalyst to form a polarisation transfer catalyst; (iii) applying a magnetic field or radio frequency excitation to (ii), such that hyperpolarisation is transferred from parahydrogen to a target molecule; (iv) introducing a target molecule containing at least at least one —N.sup.−, —O.sup.− or —S.sup.− moiety, in conjunction with a secondary binding to form a hyperpolarised agent; wherein the co-ligand is selected from the group consisting of one or more of a sulfoxide, a thioester, a phosphine, an amine, CO, an isonitrile and a nitrogen heterocycle.