“PDT is a technique with great promise that hasn’t gained clinical acceptance because of the difficulty in performing dosimetry, which is essentially determining the dose and effectiveness of delivered therapy,” explained Elliott. “Our innovation that relies on existing clinical technologies will greatly facilitate uptake of PDT through an understanding of how drugs and contrast agents are distributed to healthy and malignant tissues.”
There are two important parts to dosimetry in PDT — how much photosensitizer drug is delivered to the tumor, and how much light is deposited in the tumor. Drug delivery can be measured with fluorescence imaging, which is not a conventional tool in managing pancreatic cancer because it requires special equipment and expertise. In this study, the Dartmouth collaborators found that the values measured with dynamic contrast enhanced computer tomography (CT), a modality which is standard-of-care for patients with cancer, strongly correlated with fluorescence. Specifically, blood flow, blood volume, and permeability all correlated to fluorescence intensity measured directly from the pancreatic tissue.
In addition to the imaging challenges, Pogue’s team had to develop a preclinical model that was compatible with conventional CT and endoscopic ultrasound. Traditional models, such as mice, are too small and limit the quality of imaging. Using a rabbit model and the Pathology and Irradiator/Imaging Shared Resource at Dartmouth’s Geisel School of Medicine, they demonstrated that the rabbit model of pancreatic cancer is both reproducible and compatible with endoscopy and CT.
“Our focus on patient-centered care makes it imperative to operationalize effective palliative care that can benefit patients with late-stage pancreatic cancer being treated in typical oncology settings,” said Elliott. “PDT provides tumor control with minimal side effects. Our study demonstrates how clinicians can seamlessly integrate this important therapy into their practice without significant operational cost or burden. By using standard CT as a surrogate for dosimetry, we’ve opened up the possibility of PDT for many more patients.”
Upcoming questions for Pogue’s team include how to use CT perfusion to determine the right amounts of PDT for each patient, and whether other clinical tools such as endoscopic ultrasound can be used in resource limited settings where CT might not be available.
Jonathan T. Elliott is Lecturer in Biomedical Engineering for Global Health and Research Associate in the Optics in Medicine Laboratory at Dartmouth’s Thayer School of Engineering. Brian W. Pogue is Professor of Engineering, and of Physics Astronomy at Dartmouth College, and of Surgery at Dartmouth’s Geisel School of Medicine. Dr. Pogue’s work in cancer is facilitated by Dartmouth’s Norris Cotton Cancer Center.
“Perfusion CT Estimates Photosensitizer Uptake and Biodistribution in a Rabbit Orthotopic Pancreatic Cancer Model: A Pilot Study,” was funded by the National Institutes of Health grant PO1 CA84203/CA/NCI. Elliott is funded by a Canadian Institutes of Health Research Fellowship Award. The Pathology and Irradiator/Imaging Shared Resource at Dartmouth’s Geisel School of Medicine is open to outside investigators.