Molecular Imaging of Fibrosis for Improved Treatment Planning of Pancreatic Ductal Adenocarcinoma

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Pancreatic ductal adenocarcinoma (PDAC) is an invasive and rapidly progressive malignancy with a five-year overall survival of less than 9% despite long treatment course and recent therapeutic advances. Unfortunately, currently available imaging methods do not reliably evaluate the tumor response to neoadjuvant treatment. This further requires surgical exploration and repeated biopsies for post-chemoradiotherapy (CRT) staging. Additionally, the conventional anatomical imaging tools underrepresent the local extent of the tumor, which leads to suboptimal tumor volume measurement for definition of the field of radiotherapy. Therefore, a non-invasive imaging tool for precise evaluation of treatment response and tumor size measurement is of utmost need. High degree of fibrosis, mainly collagen type I, has been recognized as the hallmark of PDAC. Tumor-associated fibrosis further increases in response to neoadjuvant CRT and is correlated with improved outcome in patients with PDAC. Building on this knowledge, the current proposal aims to develop an image-guided paradigm for improving tumor delineation and monitoring treatment response in PDAC using a novel collagen I specific PET imaging probe, 68Ga-CBP8. This project, if successful, paves the way to provide a non-invasive and more accurate imaging tool to guide clinicians with optimized treatment planning, reduced cost of care and side effects of repeated invasive procedures, and ultimately improved outcome. We hypothesize that 68Ga-CBP8 PET imaging is a reliable and repeatable method that specifically targets and quantifies PDAC-associated fibrosis. Using the dynamic 68Ga-CBP8 PET imaging and kinetic modeling, we hypothesize that imaging PDAC can be optimized for static imaging with much shorter acquisition time. In our second aim of the grant, we hypothesize that 68Ga-CBP8 PET imaging precisely quantifies the increased PDAC fibrosis following neoadjuvant CRT and thereby could be used as a surrogate of treatment response. Lastly, we will explore whether 68Ga-CBP8 PET imaging results in more precise tumor delineation by providing more accurate gross tumor volume measurement compared to the conventional CT or MRI when correlated to the tumor size on histopathology gold standard. This research will be performed by Dr. Shadi Abdar Esfahani, a nuclear medicine and abdominal radiologist at Massachusetts General Hospital. She will be exceptionally mentored by Dr. Peter Caravan, a pioneer in PET/MR molecular imaging of fibrosis, and co-mentored by Dr. Kenneth Tanabe, a pancreas surgeon and leading expert in clinical trials and biomarker validation for pancreatic cancer. Building upon the strong clinical experience and solid pre-clinical research on molecular imaging of cancer models, Dr. Esfahani’s goal is to become an independent physician-scientist by developing a program for translational, quantitative PET/MR imaging of novel cancer biomarkers with the ultimate goal of improving clinical care and outcome. This K08 award will provide her with the training and mentorship needed to achieve independence and apply for her first R01.