Urea-Based PSMA PET Imaging Agents With Fast Blood Clearance
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Solution Overview
Problem
Current diagnostic tests for prostate cancer, such as the PSA test, are unreliable and invasive, and existing PET tracers for prostate cancer have low tumor-to-muscle ratios due to high blood activity and prolonged biologic half-life, limiting their effectiveness in detecting and grading prostate cancer.
Innovation Solution
Development of substrate-based PET imaging agents, specifically urea-based PSMA tracers labeled with [F18] via click chemistry, which provide fast radiosynthesis and improved PK/clearance profiles, allowing for non-invasive detection and grading of prostate cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mAb PET tracers are used for prostate cancer imaging, then diagnostic capability is provided, but clearance is low due to prolonged biologic half-life resulting in high blood activity and low tumor-to-muscle ratios
Solution Approach 1:
The patent changes the molecular class parameter from antibody-based tracers to small molecule urea-based tracers. This fundamental parameter change results in dramatically improved pharmacokinetic properties including faster clearance and shorter biologic half-life, while maintaining or improving diagnostic capability through high affinity binding to PSMA.
Solution Approach 2:
The patent employs small molecule tracers with short biologic half-lives instead of long-lived antibody tracers. These short-living tracer molecules provide the necessary diagnostic information quickly and are cleared rapidly from the system, reducing background noise and improving image quality without requiring long-term retention.
2Quantity of substance
If PSA test is used for prostate cancer screening, then tumor marker detection is achieved, but reliability is low due to elevated levels for non-cancer reasons and inability to diagnose aggressive cancer types
Solution Approach 1:
The patent extracts and targets a specific molecular marker (PSMA - prostate-specific membrane antigen) that is highly expressed on prostate cancer cells, particularly aggressive types. This extraction of a more specific target from the general PSA approach enables direct visualization of cancer cells through PET imaging, providing superior diagnostic accuracy and the ability to detect aggressive cancer types that PSA cannot identify.
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 PET imaging agents offer enhanced tumor-to-muscle ratios and improved diagnostic accuracy, enabling effective detection and grading of prostate cancer without invasive procedures.
Implementation Method 1
positron emission tomography (PET)... radiopharmaceuticals used in PET... labeled with [F18]
Implementation Method 2
positron emission tomography (PET)... PET imaging agents
Implementation Method 3
labeled with [F18] via click chemistry
Data Source
AI summary
Compounds for targeting and agents for imaging, prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging.