Molecular Imaging Methods for the Detection of Pancreatic Ductal Adenocarcinoma
NCI U01 - Principal Investigators: Andrei Iagaru, MD; Walter Park, MD
As part of the Pancreatic Cancer Detection Consortium, we aim to drive biomarker development and validation by establishing standardized biorepositories of high-risk individuals, and by evaluating two innovative molecular imaging strategies to detect pancreatic ductal adenocarcinoma (PDAC) much earlier than is currently possible. We have previously studied two different molecular imaging approaches for early cancer detection. The first approach involves contrast-enhanced ultrasound (CEUS) using micron-sized microbubbles. We have shown that CEUS targeted to a vascular endothelial growth factor receptor type 2 (VEGFR2; also called kinase insert domain receptor, KDR) can detect sub-centimeter PDAC lesions in a transgenic mouse model. The second approach focuses on a novel positron emission tomography (PET) tracer that selectively binds to integrin αvβ6, a cell surface receptor that is overexpressed in PDAC. In both approaches, a clinical grade agent with an FDA IND exists to allow first-in-human clinical studies for earlier detection of PDAC.
Our scientific team has broad complementary expertise in pancreatology, abdominal radiology, nuclear medicine, statistics, and pancreatic pathology. Our goals are to 1) collaboratively develop a standardized annotated biorepository with longitudinal follow-up of patients at high risk for PDAC; 2) perform first-in-human clinical trials to determine the feasibility, efficacy, and safety of KDR-targeted molecular CEUS in patients with resectable PDAC; 3) perform a first-in-human clinical trial to determine the feasibility, efficacy, and safety of αvβ6-targeted PET-CT in patients with PDAC; and 4) begin prospective pilot clinical trials using KDR-targeted molecular CEUS in patients at high risk for PDAC. In all trials, we will collect bio-specimens to support future integration of these imaging approaches with novel circulating biomarkers. The success of these first-in-human trials and systematic banking of biospecimens will support further collaborative studies for the earlier detection of PDAC.