F-18 Imidazopyridine PET Tracers for c-Abl Brain Imaging
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Solution Overview
Problem
Current methods do not effectively investigate the expression level of c-abl in live Parkinson's disease patients, which is crucial for understanding its role in disease progression and therapeutic targeting.
Innovation Solution
Development of fluorine-18 radiolabeled imidazopyridine compounds as PET tracers that selectively target c-abl for in vitro and in vivo imaging, providing a method to visualize brain abnormalities and neural injury.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional imaging methods are used, then structural information can be obtained, but molecular-level information about c-abl expression cannot be visualized
Solution Approach 1:
The patent introduces fluorine-18 radiolabeled imidazopyridine compounds as intermediary PET tracers that selectively bind to c-abl kinase. These tracers serve as mediators between the imaging system and the target protein, enabling visualization of c-abl expression and phosphorylation status in live PD patients through positron emission tomography.
Solution Approach 2:
The patent utilizes changes in biochemical parameters - specifically, the phosphorylation state of c-abl at tyrosine residues (Y412 and Y214) - as detectable markers. By targeting the phosphorylated form of c-abl rather than the total protein, the imaging method can detect active kinase states and disease progression markers in real-time.
2Reliability
If therapeutic agents targeting c-abl are developed, then disease progression can be blocked, but expression level verification in live patients remains unachievable
Solution Approach 1:
The PET imaging method provides real-time feedback on c-abl expression and activation status in live patients. This feedback mechanism allows verification of therapeutic response by monitoring changes in tracer binding signal intensity before and after treatment, enabling dynamic adjustment of therapeutic strategies.
Solution Approach 2:
The patent replaces traditional mechanical/biopsy-based sampling methods with non-invasive radiotracer imaging. Instead of requiring tissue biopsies or post-mortem analysis to measure c-abl levels, the method uses molecular imaging to visualize and quantify protein expression and phosphorylation status in living patients.
3Adaptability or versatility
If fluorine-18 radiolabeled compounds are synthesized, then PET imaging capability is provided, but the complexity of compound synthesis and radiolabeling increases
Solution Approach 1:
The patent develops a versatile PET tracer platform based on imidazopyridine compounds that can target multiple aspects of c-abl biology - including total protein expression, phosphorylation status at different tyrosine residues, and kinase activity. This multi-functional tracer system can provide different biological insights by varying the tracer structure while maintaining the same core imaging capability.
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 compounds provide a means to visualize c-abl expression and activity in the brain, potentially aiding in the diagnosis and treatment of neurodegenerative diseases like Parkinson's disease.
Implementation Method 1
positron emission tomography (PET) is a nuclear imaging methodology that detects pairs of gamma rays emitted indirectly by a positron-producing radionuclide
Implementation Method 2
detects pairs of gamma rays emitted indirectly by a positron-producing radionuclide
Implementation Method 3
The IC50's for c-abl catalytic inhibition of each cold compounds, Formula IIA and IIB are in the range of 0.59 nM to 10 nM
Implementation Method 4
c-abl is a potential therapeutic target for α-synucleinopathy, Parkinson disease, Alzheimer disease, ALS, Dementia with Lewy body and MSA
Data Source
AI summary
The present disclosure relates to [18F]-labeled imidazopyridine derivatives or salts thereof as positron emission tomography (PET) radiotracers suitable for imaging the stress-signaling non-receptor tyrosine kinase c-abl, and their use in in vivo diagnosis, preclinical and clinical imaging, patient stratification on the basis of mutational status of c-abl and assessing response to therapeutic treatments. The present disclosure further relates to the use of [18F]-labeled imidazopyridine derivatives as PET radiotracers. The disclosure also provides a process for the radiosynthesis of [18F]-labeled imidazopyridinederivatives.