Multivalent Fluorescent Tracer Synthesis Cost Reduction

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Solution Overview

Problem

Current fluorescent tracers for surgical imaging in the near-infrared range are costly due to the high expense of fluorophores and inefficient synthesis processes, limiting their application and increasing toxicity.

Innovation Solution

A method for synthesizing a fluorescent tracer using a modified fluorophore with a spacer arm and a cyclic decapeptide framework, allowing for the attachment of targeting molecules and reducing synthesis costs by using less expensive commercial fluorophores and simplifying the synthesis process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If expensive fluorophores and complex synthesis processes are used, then tracer performance and targeting capability are improved, but production cost increases and toxicity increases

Engineering Contradiction:
Improvetracer performanceVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces expensive, complex fluorophores with cheaper, commercially available alternatives that can be synthesized more simply. The use of less expensive materials directly reduces both production cost and potential toxicity, while maintaining the essential fluorescent imaging function through proper molecular design and conjugation strategies.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent optimizes the chemical and physical parameters of the tracer components, including selecting fluorophores with appropriate emission wavelengths for near-infrared imaging and adjusting the stoichiometry and conjugation methods to achieve optimal targeting performance. This allows using simpler, cheaper materials while maintaining or improving tracer effectiveness.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If expensive fluorophores and complex synthesis processes are used, then tracer performance and targeting capability are improved, but manufacturing cost increases

Engineering Contradiction:
Improvetracer performanceVSAvoidproduction cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent explicitly adopts cheaper fluorophores and simplifies the synthesis pathway, directly addressing the high manufacturing cost issue. By using commercially available, less expensive materials and reducing the number of synthesis steps, the patent makes the tracer more economically viable for clinical applications.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent divides the tracer development into modular components: a standardized cyclic decapeptide framework for targeting, separately synthesized fluorophore modules, and defined conjugation protocols. This modular approach allows independent optimization of each component and simplifies manufacturing, reducing overall production cost while maintaining performance.

Inventive Principle:
Principle #1Segmentation

3Reliability

If complex synthesis processes are used, then tracer performance is improved, but synthesis time and process complexity increase

Engineering Contradiction:
Improvetracer performanceVSAvoidsynthesis process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs a modular design where the cyclic decapeptide framework is synthesized separately and then conjugated to the fluorophore. This segmentation allows each component to be optimized independently and simplifies the overall synthesis process, reducing the number of steps required while maintaining the integrity and performance of the final tracer.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary synthesis and characterization of the cyclic decapeptide framework and fluorophore components before final conjugation. This preliminary action allows optimization of each component separately and ensures that the conjugation step can be performed efficiently with predetermined parameters, reducing overall process complexity.

Inventive Principle:
Principle #10Preliminary action

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 new tracer achieves efficient targeting of integrin αvβ3 with reduced toxicity and lower production costs, maintaining high affinity and tissue distribution similar to existing tracers while eliminating unnecessary synthesis steps.

Implementation Method 1

a fluorophore (4) comprising a carbon chain (4a) comprising at least one sequence of at least three carbon-carbon covalent double bonds such as to permit delocalization of the electrons of the double bonds when the fluorophore is excited by light radiation so as to fluoresce with an emission peak between 770 nm and 870 nm

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

permit delocalization of the electrons of the double bonds when the fluorophore is excited by light radiation

Methodology Applied
Scientific EffectElectron delocalization:

Implementation Method 3

a targeting set (3) of integrin comprising at least two identical targeting molecules (3a) comprising cyclic pentapeptides, the peptide sequence of the pentapeptides targeting an integrin comprising the amino acid residues [Arginine - Glycine - Aspartic acid-] (RGD)

Methodology Applied
Scientific EffectMolecular binding:

Data Source

PatentEP3302576B1Multivalent targeting fluorescent tracer in the near infrared range for optical imaging
Publication Date: 2021.04.28 FLUOPTICS
  • EP3302576B1 patent drawingFigure 1
  • EP3302576B1 patent drawingFigure 2~5c
  • EP3302576B1 patent drawingFigure 3

AI summary

The invention relates to a fluorescent tracer (Tf) for targeting tumors, comprising: - at least a first fluorophore (4) which fluoresces in a wavelength range of between 700 and 1000 nm, - a targeting assembly (3) which comprises at least two identical targeting molecules (3a), and - a cyclic oligopeptide (1): - configured so as to define a mean plane (Pm) defining an upper first face (Fs) and a lower second face (Fi), - comprising at least a lysine first amino acid residue (Ki) on the lower second face (Fi), - the targeting molecules (3a) being attached to the upper first face (Fs) of the mean plane (Pm), - the fluorophore (4) being attached to the lower second face (Fi) of the mean plane (Pm) via a spacer arm (8) connecting a carbon of the sequence of the at least three double bonds and the lysine amino acid residue (Ki) of the oligopeptide (1).