Fc:TβRII PET Radiotracer for Low-Background TGFβ Detection
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Solution Overview
Problem
Current PET radiotracers for TGFβ detection suffer from high background noise, prolonged biological elimination, slow radioactive decay, and radiation safety concerns, limiting their effectiveness in measuring TGFβ levels in the tumor microenvironment for cancer treatment monitoring.
Innovation Solution
Development of a recombinant Fc:TβRII PET radiotracer using the TGFβ type II receptor extracellular domain fused with a solubilizing Fc domain, which utilizes 64Cu for improved tumor penetration and pharmacokinetic properties, reducing background noise and radiation exposure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If radiolabeled antibodies are used for TGFβ detection, then TGFβ levels can be measured, but background noise increases and detection precision deteriorates
Solution Approach 1:
The patent segments the antibody structure by using only the Fc domain instead of the full-length antibody. This segmentation reduces the molecular size, enabling renal clearance and reducing background noise while maintaining the ability to detect TGFβ through the radiotracer signal.
Solution Approach 2:
The patent changes the molecular weight parameter by using the Fc domain (approximately 50 kDa) instead of full-length antibodies (150 kDa). This parameter change allows the radiotracer to be filtered by the kidneys, reducing background noise and improving measurement precision.
2Reliability
If full-length antibodies are used as radiotracers, then TGFβ can be detected, but biological elimination is prolonged
Solution Approach 1:
The patent segments the antibody into the Fc domain portion, which has a smaller molecular size that allows for faster renal clearance. This segmentation reduces the biological elimination time from days to hours, improving the timing and reliability of TGFβ detection.
3Measurement precision
If 89Zr is used for radiotracing, then TGFβ imaging can be performed, but radiation safety concerns increase
Solution Approach 1:
The patent changes the radionuclide parameter from 89Zr (78.4-hour half-life, high-energy gamma decay) to 64Cu (12.7-hour half-life, lower radiation dose). This parameter change reduces radiation exposure and safety concerns while maintaining sufficient imaging capability for TGFβ detection.
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 Fc:TβRII radiotracer provides selective and quantitative TGFβ detection with enhanced tumor penetration and faster clearance, improving imaging accuracy and safety for cancer treatment monitoring.
Implementation Method 1
64Cu decays primarily via electron capture, beta-decay, or positron emission
Implementation Method 2
64Cu decays primarily via electron capture, beta-decay, or positron emission
Implementation Method 3
Active TGFβ binds to the extracellular domain of the TGFβ type II receptor (TβRII), triggering downstream signaling
Implementation Method 4
a TβRII extracellular domain is fused with a solubilizing Fc domain to develop a TGFβ-specific Positron Emission Tomography (PET) radiotracer
Implementation Method 5
Antibody fragments have many qualities that make them superior for PET radiotracers. Due to their smaller size, antibody fragments can penetrate further into dense tumor tissue than full-length antibodies
Data Source
AI summary
Recombinant proteins that specifically bind TGFβ are disclosed. The recombinant proteins include a transforming growth factor beta (TGFβ) binding domain and an antibody Fc fragment. Also disclosed are compositions that include the disclosed recombinant protein, and methods of using such compositions for detecting TGFβ in a subject.