Clinical Application of Molecular Imaging
to Oncology
Team Leader:
- Michael V. Seiden, M.D., Ph.D.,
Massachusetts General Hospital
Key Investigators:
- Arlan Fuller, M.D., Massachusetts General Hospital
- Jeffrey G. Supko, Ph.D., Massachusetts General Hospital
- Debra Bell, M.D., Massachusetts General Hospital
- Mukesh G. Harisinghani, M.D.,
Massachusetts General Hospital
Team Disciplines:
Medical Oncology, Gynecologic Oncology, Pathology, Pharmacology, Radiology
Abstract
Molecular imaging in oncology offers the opportunity to not only improve the detection of disease but also to provide unique molecular characterization of biologic processes within the malignancy or the surrounding supportive tissue. This information, obtained in real time and through non-destructive technology, offers the ability to better understand the biology of cancer and to more intelligently select and monitor the effects of therapeutics on a specific tumor. Ovarian cancer and pancreatic are both highly lethal and common malignancies that both lack effective screening techniques. Both malignancies tend to spread early in their natural history to the peritoneal cavity and such spread greatly impacts prognosis and in the case of pancreatic cancer, surgical management. Current imaging techniques such as magnetic resonance imaging (MRI), computed axial tomography (CAT) scan, and positron emission tomography (PET) scan are unable to discern sub-centimeter tumors due partly to tumor size. Effective imaging of small tumors using these technologies is also hampered by the mobility of intraperitoneal surfaces such as loops of intestine that impedes optimal signal acquisition. Laparoscopy or laparotomy is the current standard approach for evaluating the peritoneal cavity in ovarian and pancreatic cancer patients although both techniques have limited capability of detecting sub-millimeter disease. The clinical management of both malignancies would be vastly improved by the development of imaging technologies that allow detection and characterization of very small volume intraperitoneal tumor. This proposal to the Doris Duke Foundation describes the development, testing, and use of both novel imaging equipment and novel imaging agents to better evaluate the peritoneal cavity in individuals with either ovarian cancer or clinically localized pancreatic cancer. Specifically this will include the construction of laparoscopic imaging equipment and associated software that will allow simultaneous inspection of the peritoneal cavity in both white light and in the near infrared spectrum. The inspection in the near infrared will allow the detection of near infrared imaging agents designed to specifically identify small tumors and to provide biologic characterization of the tumor. The testing the imaging system and the imaging agents will occur through a series of clinical trials enrolling women with ovarian cancer and individuals with ‘localized’ pancreatic cancer at the Massachusetts General Hospital. Execution will involve a team of medical oncologists, gynecologic oncologists, and general surgeons along with a pharmacologist, pathologist, and molecular biologist. Incorporated into these trials will be pharmacology of novel near infrared imaging agents that are designed to specifically detect tumor-associated proteases. In addition, the program will include a thorough pathologic evaluation of tumors identified by the various imaging agents to correlate optical signal with biologic characteristics of the tumor. Three industrial collaborators will aid the project with expertise in laparoscope design and construction, optical engineering, and probe construction. Although the specific clinical scenarios in which this technology will be applied vary, the technology is positioned to more intelligently determine the best surgical and systemic approaches to the treatment of both ovarian and pancreatic cancer. In addition, use of molecularly targeted near infrared probes potentially allows evaluation of therapeutic efficacy of various anti-angiogenic agents in real time in situ. It is likely that this new imaging technology will lead to changes in the clinical management of ovarian and pancreatic cancer by the conclusion of the project in 2010.