Non-nutritive Sweeteners as MRI and PET Imaging Agents
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Solution Overview
Problem
Current imaging methods, such as PET and MRI, face challenges in accurately detecting tumors due to high background signal from healthy tissues, leading to false negatives and the need for radiolabeled agents that are contraindicated for patients with renal insufficiency or diabetes.
Innovation Solution
The use of non-nutritive sweeteners like sucralose as imaging agents, which do not cross the blood-brain barrier and show no toxicity at high doses, allowing for effective MRI and PET imaging without radioactive ligands or glucose, thereby reducing false positives and negatives by accumulating in tumors due to enhanced permeability and retention.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If FDG-PET is used to detect tumors, then tumor detection capability is improved, but background signal from healthy tissues increases causing false negatives
Solution Approach 1:
The patent changes the fundamental parameter of the imaging agent from FDG (glucose analog) to non-nutritive sweeteners (sucralose, saccharin, cyclamate). These sweeteners do not cross the blood-brain barrier and are not metabolized by healthy tissues, thereby eliminating the background signal problem while maintaining tumor detection capability through enhanced permeability and retention in tumor tissues.
Solution Approach 2:
The patent employs non-nutritive sweeteners that can be administered repeatedly without accumulation of harmful effects. Unlike radiolabeled agents that require careful dosing and have limited repeat scan capability, these sweeteners provide safe, repeatable imaging without the constraints of radiolabel half-lives or cumulative toxicity.
2Measurement precision
If radiolabeled agents are used for PET imaging, then imaging capability is improved, but patient safety is compromised for those with renal insufficiency or diabetes
Solution Approach 1:
The patent uses non-nutritive sweeteners that are safe for patients with renal insufficiency and diabetes. These sweeteners do not require radiolabeling, eliminating the safety concerns associated with radioactive agents in vulnerable patient populations while maintaining effective imaging capability.
Solution Approach 2:
The patent fundamentally changes the chemical composition of the imaging agent from radiolabeled compounds to non-radiolabeled non-nutritive sweeteners. This parameter change eliminates the harmful effects of radiation exposure in patients with renal insufficiency or diabetes while preserving the ability to detect tumors through their enhanced uptake and retention of the sweetener.
3Measurement precision
If GlucoCEST is used to study tumors, then tumor visualization is improved, but tumor-specificity is reduced due to metabolism by both tumors and healthy tissue
Solution Approach 1:
The patent changes the imaging agent from D-glucose (which is metabolized by both tumors and healthy tissue) to non-nutritive sweeteners (sucralose, saccharin, cyclamate) that are not metabolized by healthy tissues. This parameter change provides tumor-specificity because only tumor tissues with disrupted blood-brain barrier and enhanced permeability can accumulate the sweetener, while healthy tissues show no uptake.
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
This approach enables clear tumor visualization with negligible background contrast, improving the monitoring of tumor relapse and treatment efficacy while being safe for patients with certain conditions, and can be used in both MRI and PET imaging.
Implementation Method 1
accumulating in tumors due to enhanced permeability and retention
Implementation Method 2
obtaining one or more test CEST MRI image of said patient subsequent to the administering step (ii)
Implementation Method 3
administering an effective amount of a non-nutritive sweetener comprising one or more radiolabels
Data Source
AI summary
The present disclosure relates to magnetic resonance imaging (MRI) methods comprising (i) obtaining a baseline chemical exchange saturation transfer (CEST) MRI image of a patient, (ii) administering an effective amount of a non-nutritive sweetener to the patient, and (iii) obtaining one or more test CEST MRI image of the patient subsequent to the administering step (ii); wherein the step (i) and (iii) acquisition parameters are substantially the same. The non-nutritive sweetener may include a natural or artificial sugar alcohol, polyol, or combinations or derivatives thereof.