Selective Radiolabelled mGluR2/3 Ligands for PET Imaging

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Solution Overview

Problem

Current positron emission tomography (PET) radiotracers are inadequate for effectively imaging and quantifying Group II metabotropic glutamate receptors (mGluR2 and mGluR3) in tissues, necessitating the development of improved radiolabelled compounds for precise imaging and therapeutic targeting.

Innovation Solution

Development of novel radiolabelled mGluR2/3 ligands, specifically compounds of Formula (I) and their pharmaceutically acceptable salts or solvates, which are selectively radioactive and suitable for PET imaging, allowing for precise imaging and quantification of mGluR2/3 receptors in tissues and cells using positron-emission tomography.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current PET radiotracers are used for imaging, then general tissue imaging is possible, but selective imaging and quantification of mGluR2/3 receptors cannot be achieved

Engineering Contradiction:
Improvereceptor quantification precisionVSAvoidreceptor imaging reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies local quality by designing radioligands with specific molecular structures (Formula I) that have selective affinity for mGluR2/3 receptors. The radioligand comprises a specific ligand structure combined with a positron-emitting radionuclide, creating a tracer that locally targets and binds to mGluR2/3 receptors with high selectivity, enabling precise imaging and quantification of these specific receptors while leaving other receptor types unaffected.

Inventive Principle:
Principle #3Local quality

2Adaptability or versatility

If non-selective radiotracers are used, then imaging coverage is broad, but specific mGluR2/3 receptor detection is inadequate

Engineering Contradiction:
Improvereceptor targeting specificityVSAvoidreceptor imaging resolution
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent applies parameter changes by modifying the chemical and physical parameters of the radiotracer to achieve selective mGluR2/3 receptor binding. This involves changing the ligand structure parameters (using specific chemical groups and configurations in Formula I) and radionuclide selection parameters (choosing positron-emitting isotopes with appropriate half-lives) to optimize both specificity and imaging precision for mGluR2/3 receptors.

Inventive Principle:
Principle #35Parameter changes

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 described compounds enable high-resolution imaging and quantification of mGluR2/3 receptors, facilitating improved diagnostic capabilities and potential therapeutic applications by providing selective and effective radiolabelled agents for PET imaging.

Implementation Method 1

The invention relates to novel, radiolabelled mGluR2/3 ligands, selective versus other mGlu receptors, which are useful for imaging and quantifying the metabotropic glutamate receptors mGlu2 and 3 in tissues, using positron-emission tomography (PET)

Methodology Applied
Scientific EffectPositron emission: Radioactive Decay

Implementation Method 2

using positron-emission tomography (PET) imaging system

Methodology Applied
Scientific EffectPositron annihilation:

Data Source

PatentEP3389727B1Radiolabelled mglur2/3 pet ligands
Publication Date: 2020.08.12 JANSSEN PHARMA NV
  • EP3389727B1 patent drawingFigure 1A~1B
  • EP3389727B1 patent drawingFigure 2
  • EP3389727B1 patent drawingFigure 3A~3B

AI summary

The present invention relates to novel, radiolabelled mGluR2/3 ligands, selective 5 versus other mGlu receptors, which are useful for imaging and quantifying the metabotropic glutamate receptors mGlu2 and 3 in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a mammal, in vitro or 10 in vivo and to precursors of said compounds.