Methods and compositions for cancer diagnosis
Inventors
Brentnall, Teresa A. • Willmann, Juergen Karl • Pan, Sheng
Assignees
University of Washington • Leland Stanford Junior University • University of Washington Center for Commercialization
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Publication Number
US-10857244-B2
Publication Date
2020-12-08
Expiration Date
Abstract
The present invention provides reagents and methods for detecting cancer and precancerous lesions in a patient.
Core Innovation
The invention relates to ultrasound molecular imaging for detecting cancer or precancerous lesions in a patient, or for determining a risk for cancer development. A composition of microbubbles having a plurality of anti-Thy-1 antibodies attached thereto is administered to a patient at risk, and binding complexes form between the binding molecules and targets of the binding molecules present in the neovasculature of the cancer or the precancerous lesions.
After administration, the binding complexes are detected using ultrasound molecular imaging. The presence of any number of the binding complexes greater than a control is indicative of the presence of cancer or precancerous lesions, or indicates a risk of cancer development in the patient.
The described microbubble compositions include lipid/perfluorocarbon microbubbles with antibody attachment, including possible multi-population and/or multi-marker designs. The target concept is also extended to additional vascular endothelial markers including MMRN1, MRC2 (endo180), NRP1, VCAM1, and optionally VEGFR2, with optional microbubble loading of anti-cancer therapeutics.
Claims Coverage
The partial content contains one independent claim. The independent claim recites two core inventive aspects: administering anti-Thy-1 antibody microbubbles to form binding complexes in cancer or precancer neovasculature, and detecting those complexes by ultrasound molecular imaging where complex counts greater than a control indicate cancer presence, precancer presence, or risk.
Anti-Thy-1 antibody microbubbles forming binding complexes in neovasculature
A method comprising administering a composition of microbubbles having a plurality of anti-Thy-1 antibodies attached thereto to a patient at risk of having or developing cancer, wherein binding complexes form between the binding molecules and targets present in neovasculature of the cancer or the precancerous lesions.
Ultrasound molecular imaging detection indicating cancer or risk
Detecting a presence or absence of the binding complexes using ultrasound molecular imaging, wherein the presence of any number of the binding complexes greater than a control is indicative of the presence of cancer or precancerous lesions in the patient or indicates a risk of cancer development in the patient.
Across the independent claim, inventive coverage centers on Thy-1-targeted microbubble binding complexes in tumor or precancer neovasculature and ultrasound molecular imaging of those complexes, interpreted relative to a control to indicate cancer, precancerous lesions, or risk.
Stated Advantages
Allows detecting cancer or precancerous lesions using ultrasound molecular imaging of binding complexes.
Provides a determination of risk for cancer development based on binding complexes greater than a control.
Uses Thy-1-targeted microbubbles, with reported signal reduction by competition/blocking, supporting target-specific imaging.
Documented Applications
Detection of pancreatic ductal adenocarcinoma (PDAC) neovasculature for cancer or precancer imaging, supported by elevation of Thy-1 on PDAC neovasculature versus chronic pancreatitis and normal tissue and by in vivo ultrasound signal enhancement in an orthotopic PDAC xenograft model.
Ultrasound molecular imaging for identifying cancer presence or increased risk in patients using Thy-1 binding molecules targeted to cancer or precancerous lesion neovasculature.
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