Surgery is the cornerstone of oncology treatment, and molecularly-targeted fluorescent imaging agents have the potential to guide surgical resection by highlighting the biological margins of the disease. However, development and testing of such molecular imaging agents has been lacking. The Thayer School of Engineering and Geisel School of Medicine at Dartmouth together with LI-COR Biosciences and Affibody AB announce a new Academic/Industry Partnership to establish an efficient pipeline for development and translation of molecularly-targeted agents. The five-year project is funded by the National Cancer Institute.
This groundbreaking study will use a cost-effective, risk-diluted approach for rapid development and testing of molecularly-targeted imaging agents in phase 0 microdosing studies. The microdosing studies are designed to evaluate imaging of specific targets.
“Targeting an evaluation of imaging in early human surgical trials will allow us to efficiently assess potential candidates for further development,” says Dr. Brian Pogue, lead investigator and Professor of Engineering at Dartmouth. “This approach will dramatically accelerate the paradigm shift to molecularly-guided surgical oncology. This grant will allow us to develop and test agents produced with current Good Manufacturing Practices whose primary use will be in diagnostic guidance in surgical oncology, and used at microdoses similar to nuclear medicine tracers.” The first agent will be an Affibody ® molecule targeted to the epidermal growth factor receptor (EGFR), which is overexpressed in a broad range of cancers.
“The use of Affibody’s proprietary molecules for optical imaging represents an exciting extension of our technology,” says Dr. Fredrik Frejd, CSO at Affibody. “Due to the high target specificity and favorable tissue distribution properties of Affibody ® molecules, tumors and their boundaries can be rapidly identified and characterized, which may allow for the development of image-guided surgery as a potential option for improved brain tumor treatment”.
“Imaging agents will be conjugated with IRDye 800CW (a near-infrared fluorescent dye developed by LI-COR), and compounds will be produced under cGMP conditions,” says Dr. Brad Roth, director of business development at LI-COR. The study will employ commercially available state-of-the-art surgical microscopes from Leica and Zeiss that are equipped for intraoperative fluorescence imaging.
Surgical signal detection and binding specificity will be the primary outcomes from the phase 0 trials. First-in-human studies with recurrent high-grade brain tumor patients will be pursued at Dartmouth under the direction of Dr. David Roberts, Section Chief of Neurosurgery, and Dr. Keith Paulsen, director of the Dartmouth Advanced Imaging Center. Approval for the microdosing studies will be sought under the exploratory investigational new drug (eIND) pathway at the FDA. This unique partnership brings together the intellectual property, expertise, and infrastructure needed for rapid development and clinical translation of molecularly-targeted imaging agents for fluorescence-guided surgery.