F-18 Metal Complex Labeling for Peptide Imaging

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Solution Overview

Problem

Current methods for F-18 labeling of peptides are tedious, require specialized equipment, and involve high radiation exposure, necessitating a rapid and simple method for achieving suitable specific activity and in vivo stability for PET imaging while minimizing equipment and personnel requirements.

Innovation Solution

An F-18 labeled molecule comprising an F-18 metal complex, where the metal is selected from aluminum, gallium, indium, lutetium, or thallium, is formed by reacting F-18 with the metal and attaching the F-18 metal complex to a molecule, such as a peptide, using chelating moieties like NOTA, to create a stable and high-specific-activity imaging agent.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If conventional F-18 labeling methods are used, then peptides can be labeled with F-18, but the process is tedious and requires specialized equipment and highly trained personnel

Engineering Contradiction:
Improveease of F-18 labelingVSAvoidspecialized equipment requirements
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent introduces a bifunctional chelating agent as an intermediary that first forms a stable complex with the radiometal (e.g., Ga-68, Cu-64) and then conjugates to the peptide. This two-step process simplifies the labeling procedure and eliminates the need for specialized equipment, as the chelating agent mediates between the radiometal and peptide components

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The chelating agent is pre-conjugated to the peptide before radiometal labeling, creating a pre-assembled targeting construct. This preliminary action allows the radiometal to be simply added and complexed in a final step, dramatically reducing the complexity and time of the labeling process

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If conventional F-18 labeling methods are used, then peptides can be labeled, but high levels of radiation exposure are required

Engineering Contradiction:
Improvespecific activity of labeled peptideVSAvoidradiation exposure
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent changes the radiometal isotope from conventional F-18 to alternative isotopes such as Ga-68, Cu-64, Zn-65, and In-111, which have different half-lives and decay characteristics. This parameter change allows for lower radiation exposure while maintaining adequate specific activity for imaging applications

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If F-18 is used for labeling, then high resolution PET imaging can be achieved, but the half-life is too short for manufacturing and distribution

Engineering Contradiction:
Improveimaging resolutionVSAvoidhalf-life of isotope
Core Design Contradiction:
Measurement precisionVSDuration of action of stationary object

Solution Approach 1:

The patent changes the isotope parameter from F-18 (110-minute half-life) to alternative radiometals with longer half-lives such as In-111 (2.8 days), Zn-65 (244 days), and Cu-64 (12.7 hours). This extends the duration available for manufacturing, quality control, and clinical distribution while maintaining sufficient imaging capability

Inventive Principle:
Principle #35Parameter changes

4Productivity

If F-18 labeling is performed, then imaging can be conducted, but the process requires highly trained personnel and is not suitable for routine clinical use

Engineering Contradiction:
Improveroutine clinical imaging capabilityVSAvoidpersonnel training requirements
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The bifunctional chelating agent serves as a mediator that simplifies the labeling process into straightforward steps that can be performed by clinical personnel with minimal training. The chelating agent handles the complex coordination chemistry, making the overall process accessible for routine clinical use

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The chelating agent performs multiple functions automatically: it complexes the radiometal, provides stability in vivo, and enables conjugation to the peptide. This self-service capability eliminates the need for highly trained personnel to perform complex labeling procedures

Inventive Principle:
Principle #25Self-service

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

This approach enables rapid, efficient, and stable F-18 labeling of peptides, reducing the need for specialized equipment and personnel, while providing high specific activity and in vivo stability for effective PET imaging, particularly for diagnosing diseases like cancer and autoimmune disorders.

Implementation Method 1

reacting the F-18 with the metal to form an F- 18 metal complex

Methodology Applied
Scientific EffectCoordination chemistry: Chemical Bonding

Implementation Method 2

attaching the F-18 metal complex to the molecule to form one or more F-18 labeled molecules

Methodology Applied
Scientific EffectChelation: Chemical Bonding

Data Source

PatentEP3020419B1Improved methods and compositions for f-18 labeling of proteins, peptides and other molecules
Publication Date: 2019.12.11 IMMUNOMEDICS INC
  • EP3020419B1 patent drawingFigure 1
  • EP3020419B1 patent drawingFigure 2
  • EP3020419B1 patent drawingFigure 3

AI summary

The present invention concerns an F-18 labeled molecule comprising an F-18 metal complex attached to the molecule for use in a method of F-18 imaging by positron emission tomography (PET).