Fluorescent Probes for the Detection and Evaluation of Occult Ovarian Cancer
Team Leader:
Michael V. Seiden, M.D., Ph.D.,
Massachusetts General Hospital
Key Investigators:
Arlan Fuller, M.D., Massachusetts General Hospital; Ralph Weissleder, M.D., Ph.D., Massachusetts General Hospital; Richard Penson, M.D., Massachusetts General Hospital; Debra Bell, M.D., Massachusetts General Hospital; Neil Horowitz, M.D., Massachusetts General Hospital
Team Disciplines:
Medical Oncology, Gynecologic Oncology, Radiology, Medical Physics, Pathology
Abstract
Standard examination for ovarian cancer involves the use of a 300mm long, 5mm diameter cylindrical lens assembly (laparoscope) projecting onto a visible spectrum charge coupled device (CCD), permitting the surgeon to image and survey the peritoneal cavity. However, sub-clinical disease goes undetected because it is not adequately imaged in the visible spectrum.
In the last several years, investigators have shown that classical imaging can be greatly enhanced by the use of reagents, which react with occult tumor and show the presence of very small tumors by signaling molecular events which are characteristic of cancer.
Essentially these molecular reagents, or molecular probes, can be made to detect several mechanisms as "markers" of cancer proliferation, such as the growth of abnormal blood vessels, the ability to subvert standard processes of cell death (apoptosis), the over-expression of growth factors and the breakdown of normal communication, or signal transduction, between elements of cell regulation.
In this work, we create a broad imaging platform by adding an infra-red channel, which is overlayed and co-registered with the standard visible optical image.
By injecting a small amount of indocyanine green (ICG), we see the notable retention of this common ophthalmic marker in abnormal tissue due to the micro-vessel density in tumor. Many similar bio-markers have been shown to specifically infer the molecular signatures of disease. ICG is made to fluoresce by near-infrared peak excitation at ~805nm using either a broadband or laser diode source. The characteristic emission at ~835_nm is captured in a secondary, devoted infra-red camera and combined and co-registered with the standard visible signal.
Biopsy guided by this method is anticipated to confirm that the combined visible and near-infrared system can locate tumor and suggest underlying causes otherwise invisible in standard practice.