Pancreatic Ductal Adenocarcinoma Targeted Ultrasound Contrast Agent Development

DESCRIPTION provided by applicant 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 months of patients with stage I disease survive 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 Thy 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 Thy and showed in a mouse model that contrast enhanced ultrasound could detect pancreatic tumors andlt mm in size This PI has also identified a peptide that binds to both murine and human Thy The second and corresponding PI on this project developed the worldandapos s selling ultrasound contrast agent and the chemist on this project previously developed the first clinical grade molecularly targeted contrast agent to enter clinical trials The overall goal of this grant proposal is to develop a novel clinically translatableThy targeted ultrasound contrast agent to improve visualization and earlier detection of PDAC thereby improving overall survival of patients with PDAC We will create bioconjugates of the peptide to Thy incorporate them into ultrasound contrast agents microbubbles confirm binding to Thy in vitro and then confirm efficacy in murine models of PDAC Because PDAC often arises in the setting of chronic pancreatitis we will also confirm that the Thy targeted ultrasound contrast agent discriminates between PDAC and chronic pancreatitis The new clinical grade Thy targeted contrast agent can enter formal development as a new drug candidate in Phase II 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