Dual-Mode MRI and Fluorescence Imaging Agents for Metal Ion Detection
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Solution Overview
Problem
Current methods for detecting metal ions in living biological systems are limited by irreversible precipitation, photobleaching, high background signals, and insufficient cell membrane permeability, making it difficult to study metal ion homeostasis and its role in health disorders like Alzheimer's disease and cancer.
Innovation Solution
Development of MRI or optical agents comprising a chelator group with an aromatic heterocycle and a binding moiety that can bind analytes, allowing for shifted signals upon interaction, enabling detection of metal ions like zinc and calcium within cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescence imaging techniques are used for metal ion detection, then spatial resolution is improved, but penetration depth and lateral range are limited
Solution Approach 1:
The patent creates imaging agents that can function in both fluorescence imaging and MRI modalities. The agents contain fluorescent moieties for high-resolution optical imaging and paramagnetic metal ions for MRI penetration, allowing the same agent to provide both spatial resolution and deep tissue penetration capabilities
Solution Approach 2:
The imaging agents are composite structures combining organic fluorescent compounds with paramagnetic metal ions (such as gadolinium or manganese). This composite approach integrates the high spatial resolution of fluorescence with the deep penetration capability of MRI, resolving the contradiction between these two parameters
2Measurement precision
If MRI contrast agents with paramagnetic metal ions are used, then sensitivity is improved, but cell membrane permeability is insufficient
Solution Approach 1:
The patent designs imaging agents with differentiated functional regions: hydrophobic regions for membrane permeability and hydrophilic regions with paramagnetic ions for sensitivity. The agents have specific molecular structures that allow them to traverse cell membranes while maintaining their paramagnetic properties for high-sensitivity detection
Solution Approach 2:
The patent modifies physical and chemical parameters of the imaging agents, including molecular size, charge, and lipophilicity, to optimize both cell membrane permeability and paramagnetic sensitivity. By adjusting these parameters, the agents achieve adequate permeability while retaining their sensitivity-enhancing paramagnetic metal ions
3Measurement precision
If fluorescent metal ion sensors are used, then detection capability is improved, but photobleaching and high background signals occur
Solution Approach 1:
The patent introduces paramagnetic metal ions as intermediaries that transfer the detection function from fluorescent moieties to MRI detection. The paramagnetic ions serve as stable mediators that provide long-term signal stability without photobleaching, while still enabling metal ion detection through their relaxation effects on surrounding water protons
4Length of stationary object
If MRI techniques are used for deep tissue imaging, then penetration depth is improved, but spatial resolution deteriorates
Solution Approach 1:
The patent merges fluorescence imaging and MRI into a single dual-modal imaging system using the same imaging agents. The fluorescence component provides high spatial resolution for precise localization, while the paramagnetic component enables deep tissue penetration via MRI, with both functions operating simultaneously to resolve the penetration-depth versus resolution contradiction
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
These agents provide enhanced stability and cell permeability, allowing for accurate detection of metal ions in vivo, facilitating the study of their physiological roles and aiding in pathological diagnoses.
Implementation Method 1
a chelator group comprising at least one aromatic heterocycle; a binding moiety covalently attached to the chelator group
Implementation Method 2
Fluorescent metal ion sensors have been investigated
Implementation Method 3
magnetic resonance imaging (MRI) techniques can noninvasively penetrate deep into an intact, opaque object
Data Source
AI summary
The present invention generally relates to agents and compositions having MRI and/or optical signals, and methods for their use in the determination of an analyte. In some cases, an optical, MRI, or other signal produced by the agent or composition may be affected by the presence of an analyte. Some embodiments of the present invention may provide agents or compositions which are cell permeable. Examples of analytes that may be determined by the present invention include zinc ions, calcium ions, and other biological analytes.