Bifunctional Chelating Agent for Rapid 18F Peptide Labeling
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Solution Overview
Problem
Current methods for 18F labeling of peptides are time-consuming, require specialized equipment, and involve multiple purification steps, making them unsuitable for rapid and simple in vivo applications, especially for temperature-sensitive molecules and clinical settings.
Innovation Solution
A bifunctional chelating agent is used to label molecules with 18F in an aqueous medium, with optional organic solvents and stabilizing agents, allowing for rapid preparation of high-specific-activity 18F-labeled molecules that are stable under physiological conditions, and can be preloaded with aluminum for storage and later labeling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional 18F labeling methods are used, then labeling can be achieved, but the process is time-consuming and requires multiple purification steps
Solution Approach 1:
The chelating agent is pre-conjugated to the peptide or protein molecule before 18F labeling, so that when 18F is introduced, it is immediately chelated by the pre-positioned chelating group, eliminating the need for intermediate purification steps and reducing overall preparation time
Solution Approach 2:
The purification step is extracted and eliminated from the process by using a chelating agent that remains stably bound to the 18F-peptide complex, allowing direct use of the labeling mixture without HPLC purification
2Ease of manufacture
If conventional 18F labeling methods are used, then labeling can be achieved, but specialized equipment and highly trained personnel are required
Solution Approach 1:
The chelating agent performs the labeling function automatically through its inherent chemical properties, forming a stable complex with 18F without requiring specialized equipment or complex operational procedures, making the process self-contained and easier to execute
3Object-affected harmful factors
If conventional 18F labeling methods are used, then labeling can be achieved, but operator exposure to high levels of radiation increases
Solution Approach 1:
The chelating agent is pre-attached to the peptide, creating a ready-to-label complex that rapidly chelates 18F upon introduction, reducing the time operators are exposed to radiation during the labeling process while maintaining high labeling efficiency
4Loss of time
If rapid labeling is implemented, then preparation time is reduced, but stability under physiological conditions may be compromised
Solution Approach 1:
The chelating agent acts as an intermediary between the peptide and 18F, forming a stable bridge that maintains both rapid labeling kinetics and long-term stability under physiological conditions, solving the contradiction between speed and stability
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 method enables the rapid preparation of 18F-labeled molecules with high specific activity, suitable for in vivo use, reducing the need for HPLC purification and minimizing radiation exposure, while being compatible with kit formulations and temperature-sensitive molecules.
Implementation Method 1
A rapid and simple method of 18F-labeling peptides, proteins and other molecules is needed that retains in vivo stability
Implementation Method 2
The use of an organic solvent in the labeling reaction can improve the labeling efficiency
Implementation Method 3
a stabilizing agent such as ascorbic acid, trehalose, sorbitol or mannitol may be added
Implementation Method 4
Alternatively, a chelating moiety may be preloaded with aluminum and lyophilized for storage, prior to labeling with 18F
Data Source
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AI summary
The present application discloses compositions and methods of synthesis and use of 18F or 19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the labeled molecule may be used for imaging in a subject without purification after labeling.