DPP4 Radionuclide Probe for Specific Myocarditis Imaging
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Solution Overview
Problem
Current diagnostic methods for myocarditis, such as electrocardiography, serum biomarkers, and radionuclide imaging agents like 18F fluorodeoxyglucose and 18F-fluoromethyl-PBR28, lack specificity and sensitivity for detecting myocardial inflammatory foci, necessitating a non-invasive or low-invasive method with high specificity and sensitivity.
Innovation Solution
A myocarditis-targeted radionuclide molecular probe is developed, comprising a DPP4 inhibitor (e.g., Linagliptin) covalently bonded to a bifunctional chelator (e.g., p-SCN-Bn-DOTA) and coordinately bonded to a metallic radionuclide (e.g., 68Ga), allowing for high specificity and sensitivity in detecting myocardial inflammatory foci.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional diagnostic methods (ECG, serum biomarkers, echocardiography, CMR) are used, then the diagnostic process is non-invasive and easy to perform, but the sensitivity and specificity for detecting myocardial inflammatory foci are insufficient
Solution Approach 1:
The patent changes the chemical and molecular parameters of the imaging probe by using a DPP4 inhibitor as the molecular core instead of conventional probes like 18F fluorodeoxyglucose. This parameter change enables specific binding to DPP4 enzymes overexpressed in inflammatory cells, dramatically improving detection sensitivity and specificity for myocardial inflammatory foci while maintaining non-invasive imaging capabilities
Solution Approach 2:
The patent creates a composite radionuclide molecular probe by combining a DPP4 inhibitor (molecular core) with a bifunctional chelator and a radionuclide. This composite structure integrates the targeting capability of the DPP4 inhibitor with the imaging capability of the radionuclide, achieving both high specificity for inflammatory foci and high-resolution imaging
2Measurement precision
If 18F fluorodeoxyglucose is used as a radionuclide imaging agent, then the imaging can be performed non-invasively, but the probe is taken up by cardiomyocytes in large quantities, interfering with detection of cardiac inflammatory foci
Solution Approach 1:
The patent applies local quality by designing a probe with specific molecular characteristics (DPP4 inhibitor) that confers selective affinity for inflammatory cells. The probe exhibits different uptake patterns in different tissue types: high uptake in inflammatory cells expressing DPP4 and low uptake in normal cardiomyocytes, thereby eliminating the harmful interference problem
3Measurement precision
If 18F-fluoromethyl-PBR28 probe is used, then the probe can detect inflammation, but the sensitivity for detecting myocardial inflammation is inadequate and it is more suitable for detecting extracardiac inflammation
Solution Approach 1:
The patent changes the molecular target parameter from translocator protein (target of PBR28) to DPP4 enzyme. This parameter change fundamentally improves the probe's sensitivity for myocardial inflammation detection, as DPP4 is highly overexpressed in activated inflammatory cells infiltrating the myocardium, making the probe specifically adapted for cardiac inflammation detection
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 probe exhibits significant uptake in myocardial inflammatory cells and low uptake in non-target tissues, enabling high-resolution imaging for early diagnosis and therapeutic efficacy evaluation of myocarditis.
Implementation Method 1
a bifunctional chelator covalently bonded to an amino group of the DPP4 inhibitor
Implementation Method 2
a metallic radionuclide coordinately bonded to the bifunctional chelator
Implementation Method 3
The probe exhibits significant uptake in myocardial inflammatory cells
Data Source
AI summary
Disclosed are a myocarditis-targeted radionuclide molecular probe, a preparation method therefor, and an application thereof. The myocarditis-targeted radionuclide molecular probe includes a DPP4 inhibitor, a bifunctional chelator covalently bonded to an amino group of the DPP4 inhibitor, and a metallic radionuclide coordinately bonded to the bifunctional chelator. The myocarditis-targeted radionuclide molecular probe provided by the present disclosure exhibits high specificity and good targeting capability, and demonstrates significant uptake in myocardial inflammatory cells, and low uptake in non-target tissues. Characterized by high resolution and sensitivity of imaging, the myocarditis-targeted radionuclide molecular probe is applied for early diagnosis of cardiac inflammatory infiltration severity, therapeutic efficacy evaluation, prognosis assessment and the like, and has promising clinical and application prospects in the field of non-invasive nuclear medicine diagnosis and treatment as a myocarditis imaging agent.