Ascorbate formulations and methods of use as contrast agents
Inventors
Assignees
Publication Number
US-12303572-B2
Publication Date
2025-05-20
Expiration Date
2036-09-29
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Abstract
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.
Core Innovation
The invention provides compositions and methods for enhancing magnetic resonance imaging (MRI) using ascorbate (Vitamin C) as a contrast agent. The described sterile aqueous compositions contain 100 to 600 mM ascorbate and 100 to 600 mM sodium, meglumine, or a combination thereof, and are characterized by an osmolarity of 200 to 1400 mOsm/L. These compositions can also include spin-spin exchange catalysts such as reducing sugars, non-reducing sugars, carbonate, phosphate, or stability agents like chelators.
The motivation for this invention arises from the substantial limitations and health risks associated with current gadolinium-based contrast agents for MRI, which can cause nephrogenic systemic fibrosis and may result in brain deposition of gadolinium. The invention addresses the need for alternative or additional MRI contrast agents that are safer and do not require metal-based components or radioactive tracers.
Upon parenteral administration, the disclosed ascorbate formulations induce time-dependent changes in magnetic resonance (MR) signal in tissues and fluids where ascorbate is taken up or passes through. These signal changes are detectable using standard T2-weighted MRI sequences and are further quantifiable with T2 mapping. The invention includes methods for administering these formulations parenterally (e.g., intravenously, intraperitoneally), with resulting imaging possible during or up to several hours after administration, enabling detection and characterization of perfusion, metabolism, and oxidative stress without the need for radioactivity or chemical labeling.
Claims Coverage
There are two independent claims in this patent, each defining a core inventive feature involving the use of ascorbate-containing compositions as MRI contrast agents.
Method of enhancing MRI image using ascorbate and spin-spin exchange catalyst
A method comprising parenteral administration, in an MRI image-enhancing amount, of a sterile aqueous composition that includes: - 100–600 mM ascorbate, - 100–600 mM sodium, meglumine, or a combination thereof, - a spin-spin exchange catalyst, - an osmolarity of 200–1400 mOsm/L; followed by generating an MRI image of a body or body region, whereby the MRI image is enhanced.
Method using specific sodium and meglumine ratio in ascorbate composition for MRI image enhancement
A method comprising parenteral administration, in an MRI image-enhancing amount, of a sterile aqueous composition that includes: - 100–600 mM ascorbate, - 100–600 mM of a combination of sodium and meglumine in a molar or millimolar ratio of 10:90 to 90:10, - an osmolarity of 200–1400 mOsm/L; and subsequently generating an MRI image of a body or body region, whereby the MRI image is enhanced.
The inventive features described cover the administration of specific ascorbate-based formulations—defined by concentrations, osmolarity, and inclusion of sodium, meglumine, or their combination (with or without spin-spin exchange catalysts)—for the enhancement of MRI imaging.
Stated Advantages
Provides an MRI contrast agent that does not require metal-based (e.g., gadolinium or iron) contrast materials or ionizing radiation.
Enables assessment of tissue perfusion and high-resolution molecular characterization of tissue viability and metabolism analogous to 18F-FDG PET.
Uses a safe and biodegradable agent (ascorbate) with low toxicity.
Documented Applications
Magnetic resonance imaging (MRI) contrast for detection and characterization of perfusion, metabolism, and oxidative stress in human and non-human tissues.
Diagnostic studies for cancer, neurological disease (including dementia, traumatic brain injury, epilepsy), and cardiovascular imaging.
Myocardial perfusion and viability imaging as an alternative to Tc-99m-based nuclear medicine agents.
Imaging of organs or organ regions such as the brain or heart for perfusion, metabolism, and viability.
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