Near-Infrared Peptide Imaging for Microscopic Glioblastoma Margins
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Solution Overview
Problem
Current imaging techniques, such as MRI, are inadequate for detecting microscopic invading cancer cells (tentacles) in glioblastoma tumors, leading to high recurrence rates due to their inability to visualize cells that migrate away from the main tumor mass.
Innovation Solution
Development of near-infrared imaging agents comprising a targeting peptide that binds to proteolytically cleaved extracellular fragments of immunoglobulin superfamily cell adhesion molecules, linked to a near-infrared fluorophore via a natural or non-natural linkage, to specifically target and delineate cancer cells and their margins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If MRI with gadolinium contrast enhancement is used to delineate tumor borders, then the main tumor mass can be visualized, but microscopic invading cells (tentacles) that migrate away from the main tumor mass cannot be detected
Solution Approach 1:
The patent employs near-infrared fluorescent imaging agents that emit light in the near-infrared region, providing a different 'color' or wavelength range for tumor visualization compared to traditional gadolinium-based MRI. This allows specific targeting of cancer cells through fluorescent markers that bind to tumor-specific markers, enabling detection of microscopic invading cells that migrate away from the main tumor mass.
Solution Approach 2:
The patent transitions from using gadolinium contrast enhancement parameters in MRI to using near-infrared fluorescent imaging parameters. This involves changing the detection wavelength, contrast mechanism, and imaging modality to achieve superior visualization of tumor margins and invading cells through fluorescent probes that target specific cancer cell markers.
2Measurement precision
If near-infrared fluorophores are made hydrophobic or lipophilic to improve tumor cell binding, then the signal to background ratio improves for delineating cancer cells, but the complexity of the imaging agent increases
Solution Approach 1:
The patent utilizes composite imaging agents that combine near-infrared fluorophores with hydrophobic or lipophilic characteristics along with targeting peptides. These composite structures integrate multiple functional components - the fluorophore for signal generation, the hydrophobic/lipophilic moieties for membrane interaction and binding affinity, and the targeting peptide for specific cancer cell recognition - thereby achieving high signal-to-background ratios while managing structural complexity through systematic molecular design.
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 near-infrared imaging agents provide clear demarcation of tumor cells and margins, enabling precise surgical resection and potential phototherapy, with rapid and specific labeling of tumors and tumor margins, and the ability to cross the blood-brain barrier to detect metastases and invasions.
Implementation Method 1
a near-infrared fluorophore that is directly or indirectly linked to the targeting peptide or optional spacer via a natural or non-natural linkage
Data Source
AI summary
A near-infrared imaging agent includes a targeting peptide that specifically binds to and/or complexes with a proteolytically cleaved extracellular fragment of an immunoglobulin (Ig) superfamily cell adhesion molecule that is expressed by a cancer cell or another cell in the cancer cell microenvironment, an optional spacer directly linked to the targeting peptide; and a near-infrared fluorophore that is directly or indirectly linked to the targeting peptide or optional spacer via a natural or non-natural linkage.