Folate Pathway PET Tracer for Bacterial Infection Imaging
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Solution Overview
Problem
Current diagnostic methods for bacterial infections are hindered by lack of sensitivity and specificity, particularly due to the non-specific uptake of existing PET tracers like FDG, which accumulates in cells with high glycolytic activity, leading to false positives and confounding results from inflammation and cancer.
Innovation Solution
Development of a PET tracer composition comprising 4-amino-2-[18F]-fluorobenzoic acid or its salt, which selectively accumulates in bacterial cells through the folate biosynthesis pathway, allowing for precise detection and localization of infectious bacteria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If FDG is used as a PET tracer for infection imaging, then the tracer can detect cells with high glycolytic activity, but it lacks specificity and accumulates in both inflammatory cells and tumor cells leading to false positives
Solution Approach 1:
The patent targets a specific bacterial enzyme (dihydropteroate synthase) rather than general metabolic pathways. By designing a tracer that specifically binds to this bacterial enzyme through the bacterial folate pathway, the invention achieves local specificity at the molecular level, distinguishing bacterial infections from inflammatory cells and tumors that lack this specific enzyme.
Solution Approach 2:
The patent introduces a bacterial-specific folate pathway intermediate as the tracer mechanism. The tracer mimics PABA (para-aminobenzoic acid), which is a specific intermediate in the bacterial folate biosynthesis pathway. This intermediary approach allows selective targeting of bacteria through their unique metabolic pathway, avoiding uptake by human cells.
2Measurement precision
If existing PET tracers are used for bacterial infection detection, then imaging can be performed, but the signal-to-background ratio is low due to non-specific uptake
Solution Approach 1:
The tracer is designed to specifically target the bacterial folate pathway enzyme dihydropteroate synthase, creating high local concentration at the infection site while maintaining low background signal in non-infected tissues. This specific molecular targeting enhances the signal-to-background ratio by several fold compared to non-specific tracers.
3Ease of operation
If FDG-PET is used for infection diagnosis, then non-invasive imaging is achieved, but results are confounded by inflammation from other disorders and cancer
Solution Approach 1:
The patent uses a tracer that specifically targets the bacterial folate pathway, which is absent in human cells. This creates a selective intermediary mechanism where the tracer accumulates only in bacteria, allowing clear differentiation between bacterial infections and sterile inflammation or cancer, while maintaining the non-invasive PET imaging approach.
Data Source
AI summary
The present invention provides a composition comprising the compound having the structure:or a salt of the compound; 4-amino-2-[19F]-fluorobenzoic acid or a salt of 4-amino-2-[19F]-fluorobenzoic acid; and at least one acceptable carrier.