Molecular Probe for Noninvasive Pancreatic Islet Imaging
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Solution Overview
Problem
Current methods for imaging pancreatic islets are invasive and lack the ability to perform noninvasive three-dimensional imaging, which is crucial for early detection and prevention of diabetes, as the decrease in pancreatic islet cells often goes undetected until glucose tolerance abnormalities occur.
Innovation Solution
A molecular probe comprising specific polypeptides with an α-amino group labeled at the N-terminus and an amidated carboxyl group at the C-terminus, capable of binding to pancreatic islets, is used for noninvasive three-dimensional imaging via PET or SPECT, allowing for specific accumulation in pancreatic islets and reduced elimination of radioactive iodine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional imaging methods are used to detect pancreatic islets, then imaging can be performed, but the methods are invasive and cannot provide noninvasive three-dimensional imaging
Solution Approach 1:
The patent uses a molecular probe as an intermediary substance that selectively accumulates in pancreatic islets. This probe acts as a mediator between the imaging system and the target tissue, enabling noninvasive detection through blood circulation and selective uptake, thereby resolving the contradiction between noninvasive operation and imaging capability
Solution Approach 2:
The molecular probe incorporates radioactive iodine labeling that produces detectable signals through radiation detection. This signaling mechanism enables the imaging system to visualize pancreatic islets without physical intervention, achieving noninvasive three-dimensional imaging by converting biological presence into detectable physical signals
2Measurement precision
If imaging is performed to detect pancreatic islet cells, then the amount of islets can be determined, but the decrease in islet cells goes undetected until glucose tolerance abnormalities occur
Solution Approach 1:
The molecular probe enables preliminary detection of pancreatic islet cell changes before clinical symptoms appear. By circulating the probe and detecting its accumulation in islets, the system can measure islet mass reduction in the pre-diabetic stage, providing early warning before glucose tolerance abnormalities develop
Solution Approach 2:
The imaging system provides continuous feedback on pancreatic islet status through quantitative measurement of probe accumulation. This feedback mechanism allows monitoring of islet cell changes over time, enabling early detection of deterioration trends before they manifest as clinical diabetes
3Reliability
If a molecular probe is designed to target GLP-1R in pancreatic islets, then specific binding can be achieved, but the probe must overcome elimination of radioactive iodine
Solution Approach 1:
The patent modifies the molecular probe structure by incorporating amino acid residues with specific chemical properties that enhance binding affinity to GLP-1R. These parameter changes in the probe's molecular structure optimize its interaction with target receptors while maintaining stability against radioactive iodine elimination
Solution Approach 2:
The molecular probe is designed as a composite structure combining peptide components with radioactive iodine labeling. This composite design integrates the binding functionality of the peptide with the detectability and stability characteristics of the radioactive label, achieving both specific binding and reduced elimination simultaneously
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
Enables noninvasive three-dimensional imaging of pancreatic islets, facilitating early detection and prevention of diabetes by providing a method for quantifying pancreatic islet cells before glucose tolerance abnormalities arise, thereby improving diagnostic capabilities.
Implementation Method 1
a molecular probe comprising any one of the following polypeptides: a polypeptide represented by any one of the following formulae (1) to (4) and (9) to (12)... the α-amino group at the N-terminus labeled with a group represented by formula (II) below... capable of binding to pancreatic islets
Implementation Method 2
enables imaging of pancreatic islets, preferably three-dimensional imaging of pancreatic islets... by, for example, positron emission tomography (PET)
Implementation Method 3
enables imaging of pancreatic islets, preferably three-dimensional imaging of pancreatic islets... by, for example, positron emission tomography (PET) or single photon emission computed tomography (SPECT)
Implementation Method 4
GLP-1R (glucagon-like peptide-1 receptor) is being researched as a target molecule; GLP-1R is distributed in pancreatic β-cells, and is a seven-transmembrane G protein coupled receptor... a molecular probe obtained by labeling a derivative of exendin-4(9-39) as a GLP-1R antagonist
Data Source
Figure 1A~1B
Figure 2A~2B
Figure 3~4
AI summary
To provide a molecular probe for imaging of pancreatic islets. A molecular probe for use in imaging of pancreatic islets is provided. The molecular probe includes any one of the following polypeptides: polypeptides represented by the following formulae (1), (5), and (9); and polypeptides having homology with the foregoing polypeptides: Z-DLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (1) Z-DLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2 (5) B-DLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (9) where X in the formulae (1) and (5) and B- in the formula (9) indicate that an amino group is labeled with a group represented by the formula (I) below having an aromatic ring, where A represents either an aromatic hydrocarbon group or an aromatic heterocyclic group, R1 represents a substituent that contains radioactive iodine, R2 represents either a hydrogen atom or a substituent different from that represented by R1, and R3 represents any one of a bond, a methylene group, and an oxymethylene group.