Molecular probes and methods of use
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Publication Number
US-12599684-B2
Publication Date
2026-04-14
Expiration Date
Abstract
A molecular probe includes the following formula: P-L-C wherein P is a EDB-FN targeting peptide, C is a contrast agent; and L is a non-peptide linker that covalently links the peptide to the contrast agent.
Core Innovation
The disclosure provides molecular probes for cancer imaging that target EDB-FN, and optionally EDA-FN, using a peptide–non-peptide linker–contrast agent architecture (P–L–C). The targeting peptide includes peptide sequences identified as SEQ ID NOs: 1–9, and the probe architecture combines a peptide component with a non-peptide linker and a contrast agent for imaging. The contrast agent is selected from imaging agents for MRI, PET, or SPECT, including chelated metal complexes and metallofullerenes.
The non-peptide linker can include carboxamide or thioester-forming groups and can further include polymeric spacer components such as PEG/POE/dextran. The disclosure also includes chelated-metal specifications, where M is a chelated metal and at least two optional coordinate covalent bonds form coordinate covalent bonds with the chelated metal.
The document states that the probes are used to detect cancer cell location and/or distribution in tissue and can be correlated with cancer aggressiveness and therapeutic efficacy monitoring. The disclosed imaging includes detection of EDB-FN bound probe in tissue using imaging modalities including MRI, PET, and SPECT.
Claims Coverage
The partial claims include two independent claims. Across the independent claim(s), the inventive coverage centers on a chelated-metal compound with at least two coordinate covalent bond-forming dashed lines and a method for detecting cancer cells expressing EDB-FN by imaging an EDB-FN-bound chelated-metal compound.
Chelated-metal compound with at least two coordinate covalent bonds
A compound selected from a formula and salts thereof where M is a chelated metal and at least two of the dashed lines form coordinate covalent bonds with the chelated metal.
Imaging-detected EDB-FN binding correlated with cancer cell distribution
A method of detecting the presence, location and/or distribution of cancer cells expressing EDB-FN by contacting tissue with the chelated-metal compound and detecting the compound bound to EDB-FN using an imaging modality, wherein the detected presence, location and/or distribution of the compound bound to EDB-FN is correlated with the presence, location and/or distribution of EDB-FN expressing cancer cells in the tissue.
Claim coverage centers on a chelated-metal compound defined by coordinate covalent bond geometry and a method that images EDB-FN-bound compound in tissue, correlating the detected imaging distribution with EDB-FN expressing cancer cell presence, location, and/or distribution.
Stated Advantages
Strong, EDB-FN-specific T1-weighted signal enhancement.
Increased contrast-to-noise ratio (CNR) in differential imaging.
Competitive binding by excess ZD2 supports EDB-FN specificity relative to control behavior.
Higher relaxivity and robust tumor enhancement relative to ProHance for additional EDB-FN-binding peptide-Gd-DOTA conjugates.
High-relaxivity targeted imaging differentiation of aggressive TNBC versus ER-positive models with described low-dose imaging.
Minimal Gd release/retention for the peptide-conjugated gadofullerene system.
Enables detecting the presence, location and/or distribution of cancer cells expressing EDB-FN by imaging a compound bound to EDB-FN.
Provides a correlation between detected imaging distribution of the EDB-FN-bound compound and the distribution of EDB-FN expressing cancer cells in tissue.
Supports correlation of EDB-FN imaging results with cancer aggressiveness, including using a greater amount versus a control.
Documented Applications
Imaging and differentiation of prostate cancer xenografts in vivo (PC3 versus LNCaP) by EDB-FN-specific T1-weighted MRI with correlated detection of EDB-FN expression.
Detection and mapping of EDB-FN-expressing cancer cell distribution in aggressive versus ER-positive tumor models using targeted imaging with the described TNBC and ER-positive models.
PET-related extension via copper-64 labeling (described as PET precursor copper-64 labeling/extension of the agent labeling approach).
Use of comparative imaging with a clinical control agent ProHance (gadoteridol) as a benchmark in the documented imaging studies.
Assessment of EDB-FN-binding peptide candidates discovered via phage display using peptide-Gd-DOTA conjugates for tumor enhancement and imaging performance relative to ProHance.
Imaging of cancer cell location and/or distribution in tissue for cancer cells expressing EDB-FN.
Assessment of cancer aggressiveness by comparing detected/distributed EDB-FN-bound compound versus a control.
Use of imaging modalities including MRI, PET, and SPECT to detect compound bound to EDB-FN in tissue.
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