SBIR-STTR Award

?Pancreatic ductal adenocarcinoma (PDAC) is a deadly form of cancer and patient survival depends upon the stage of diagnosis. While overall survival at diagnosis is only about 4-6 months, 30-40% of patients with stage I disease survive 5 years. The best currently available diagnostic test which is routinely performed in patients at high risk for PDAC is endoscopic ultrasound (EUS). However, EUS has low specificity and poor interobserver reliability. One of the two PIs has identified and validated Thy1 as a novel, highly specific neoangiogenesis marker in patients with PDAC. In a preliminary study the PI tested an ultrasound contrast agent bearing antibodies to Thy1 and showed in a mouse model that contrast enhanced ultrasound could detect pancreatic tumors

Public Health Relevance Statement:


Public Health Relevance:
Pancreatic ductal adenocarcinoma is a particularly lethal form of cancer. Patients who are detected at early stage have much better chance of curative resection and much better overall survival but accurate tests are not yet available for detecting early stage disease. This research will develop a new ultrasound contrast agent to enable rapid and effective detection of early stage pancreatic cancer.

Project Terms:
advanced disease; Antibodies; Applications Grants; base; Binding (Molecular Function); Biological Markers; C-terminal; Cancer Etiology; Cancer Patient; Cessation of life; Chemistry; chronic pancreatitis; Clinical; Clinical Trials; clinically significant; contrast enhanced; Contrast Media; Coupling; Cysteine; Detection; Development; Diagnosis; Diagnostic Neoplasm Staging; Diagnostic tests; Disease; drug candidate; Early Diagnosis; Excision; Generations; Goals; high risk; Human; Image; Imagery; Immunoconjugates; improved; In Vitro; in vivo; in vivo imaging; Incidence; Ligands; Lysine; Maleimides; Malignant neoplasm of pancreas; Malignant Neoplasms; manufacturing scale-up; methyl 4-mercaptobutyrimidate; Microbubbles; Microbubbles Ultrasound Contrast Medium; Molecular; molecular imaging; molecular marker; Molecular Weight; Monoclonal Antibodies; mouse model; Mus; next generation; Noise; novel; novel therapeutics; Operative Surgical Procedures; Outcomes Research; Pancreas; pancreas xenograft; Pancreatic Ductal Adenocarcinoma; pancreatic neoplasm; Patients; Peptides; Phase; Phospholipids; Preparation; public health relevance; Reagent; Research; research study; Sensitivity and Specificity; Signal Transduction; Site; Specificity; Stage at Diagnosis; Staging; Sulfhydryl Compounds; Symptoms; Testing; Time; Transgenic Mice; tumor; Tumor stage; Ultrasonography; Work

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer. In most patients, detection is at an advanced stage and the outcome is poor. This project is directed towards development of a molecularly targeted ultrasound contrast agent with potential to detect early stage disease while still curable. In Phase I of this project, we incorporated the engineered human single-chain variable fragment (scFv) containing a C-terminal cysteine into maleimide-bearing phospholipid-coated perfluoropropane microbubbles (MB), and in in vivo testing of Thy1- targeted MB for PDAC detection in transgenic mice detected PDAC tumors

Public Health Relevance Statement:
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer; in most patients, detection is at an advanced stage and the outcome is poor. This project is directed towards development of a molecularly targeted ultrasound contrast agent with potential to detect early stage disease while it is still curable. In Phase I of this project, we showed feasibility and in this Phase II of the project we will complete studies that would ready the contrast agent for clinical testing.

Project Terms:
Affinity; Animals; base; Binding; C-terminal; Chemistry; Clinical Research; clinical risk; clinical translation; Clinical Trials; clinically translatable; Contrast Media; Coupled; Cyclic GMP; Cysteine; Detection; Development; Diagnosis; Disease; Dose; drug candidate; drug development; drug testing; Evaluation; first-in-human; Formulation; Human Engineering; Imagery; improved; In Vitro; in vivo; in vivo evaluation; Investigational Drugs; Investigational New Drug Application; Legal patent; Maleimides; Malignant Neoplasms; manufacturing facility; Membrane; Methodology; Methods; Microbubbles; Molecular Target; monomer; Outcome; Outcomes Research; Pancreatic Ductal Adenocarcinoma; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Phospholipids; Preparation; Procedures; Production; quality assurance; Quality Control; Reaction; Research; research clinical testing; Resources; risk minimization; Rodent; scale up; shear stress; Signal Transduction; Streptavidin; Suspensions; Testing; TimeLine; Toxic effect; Toxicology; Transgenic Mice; tumor; Ultrasonography; Validation