MRI Contrast Formulation Merging Hepatobiliary and Vascular Enhancement
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Solution Overview
Problem
Gadoxetate, a liver-specific MRI contrast agent, suffers from a poor dynamic vascular phase, leading to inadequate visualization of vascular structures and lesion characterization, particularly in the portal venous and late venous phases, compared to non-specific gadolinium chelates.
Innovation Solution
A pharmaceutical formulation comprising a first API with hepatocellular uptake and biliary excretion, and a second API with renal excretion, both as metal chelates, administered in a specific ratio and dose to enhance vascular enhancement across all phases, thereby improving liver lesion characterization and vascular biomarker profiling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a single dose of gadoxetate is used, then hepatobiliary excretion is achieved, but dynamic vascular phase enhancement is poor
Solution Approach 1:
The patent combines gadoxetate (first API) with a non-specific gadolinium chelate (second API) in a single pharmaceutical formulation. This merging allows the formulation to simultaneously provide hepatobiliary excretion enhancement from gadoxetate and dynamic vascular phase enhancement from the non-specific chelate, resolving the contradiction between these two functions that cannot be achieved with gadoxetate alone.
Solution Approach 2:
The invention creates a composite contrast agent formulation containing both gadoxetate and a non-specific gadolinium chelate in specific ratios. This composite material leverages the complementary properties of both agents: gadoxetate's liver-specific uptake and the non-specific chelate's robust vascular enhancement, achieving both hepatobiliary and vascular phase improvement in a single administration.
2Illumination intensity
If a double dose of gadoxetate is used, then vascular enhancement is improved, but gadolinium burden increases
Solution Approach 1:
The patent optimizes the ratio parameters of gadoxetate to non-specific chelate in the formulation. By adjusting this parameter, the formulation achieves adequate vascular enhancement without requiring double the standard dose of gadoxetate, thereby controlling gadolinium burden while maintaining imaging quality.
Solution Approach 2:
The non-specific gadolinium chelate acts as an intermediary agent that provides vascular enhancement, allowing the gadoxetate component to focus on hepatobiliary excretion. This intermediary approach enables adequate vascular phase imaging without increasing the total gadolinium dose required for liver-specific enhancement.
3Illumination intensity
If an additional injection of general purpose agent is given, then vascular phase is improved, but procedure complexity increases
Solution Approach 1:
The patent merges gadoxetate and a non-specific gadolinium chelate into a single pharmaceutical formulation that can be administered in one injection. This eliminates the need for sequential injections (first gadoxetate, then general purpose agent 20 minutes later), thereby reducing procedure complexity while maintaining improved vascular phase enhancement.
Solution Approach 2:
The non-specific gadolinium chelate is included in the formulation from the start, providing immediate vascular enhancement from the beginning of the dynamic vascular phase. This preliminary action eliminates the need for delayed secondary injection, simplifying the overall procedure while ensuring adequate vascular phase imaging.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulation provides sustained vascular enhancement, facilitating simultaneous assessment of vascular and delayed enhancement of liver lesions with reduced gadolinium burden, improving diagnostic accuracy and lesion detection.
Implementation Method 1
each of said first API and said second API is a metal chelate comprising a chelant and a paramagnetic metal ion
Data Source
AI summary
The present invention relates to in vivo imaging and in particular to magnetic resonance imaging (MRI). Provided by the present invention is a pharmaceutical formulation suitable for use in an MRI procedure and which offers advantages over known such formulations. A particular dose of the pharmaceutical formulation of the invention is also envisioned as well as the use of said dose in a method of in vivo imaging. This present invention provides for simultaneous administration of a liver specific agent and a second MR contrast agent that is capable of better/further enhancing the dynamic vascular phase in a patient. The method of the invention has the advantage of simplicity and patient comfort, compared to sequential injections. Furthermore, the method of the invention provides the advantage that it can enable a lower cumulative dose of contrast agents.