DESCRIPTION (provided by applicant): Pancreatic cancer is the 5th leading cause of cancer death in men and women, and ovarian cancer is the fourth leading cause of cancer death in women. In both cases, even patients who have a remission at the time of completion of initial treatment will experience recurrence due to micrometastatic disease. The ability to detect disease at this level may identify a group of patients in whom standard initial treatment will be inadequate in long-term control of the disease and would help guide treatment and spare patients the morbidity of ineffective treatments. We propose the first trial in patients of one of a new class of "smart agents" that offers the ability to detect occult micrometastatic disease and further, to provide proof of principle of the ability to evaluate molecular processes occurring in cancers. Bringing VM110 to the first trial in patients is possible through an academic-industrial partnership between FCCC and VisEn. VisEn has developed a class of imaging agents that can detect biochemical activities specific to cancer cells in animals with the use of near-infrared imaging. VM110 has been specifically developed for use in detection of cancer activity in the clinical setting in patients. Throughout the next five years, we will confirm the safety and optimal dosing schedule in preclinical models, confirm efficacy in those models and conduct the first clinical trial in patients with ovarian or pancreatic cancer to evaluate the safety, toxicity and efficacy of VM110 and near-infrared imaging in the detection of micrometastatic disease. PUBLIC HEALTH RELEVANCE: Pancreatic and ovarian cancers have a high case-fatality rate due to the early spread of disease to the peritoneal cavity. We are currently unable to detect the spread of micrometastases in patients with apparently localized disease at diagnosis, but tools that could help us identify such occult disease would improve the initial treatment of patients, particularly in the case of patients with pancreatic cancer in sparing them the morbidity of ineffective aggressive surgery and improving the chance of disease control in such patients. The use of VM110 and near-infrared (NIRF) imaging offers the opportunity to identify occult micrometastatic disease and is the first step in studying molecular processes occurring in cancers in real- time, enabling us to learn more about disease processes, and ultimately better match or develop molecularly targeted personalized treatment for patients with cancer.

Relevance to Public Health: Pancreatic and ovarian cancers have a high case-fatality rate due to the early spread of disease to the peritoneal cavity. We are currently unable to detect the spread of micrometastases in patients with apparently localized disease at diagnosis, but tools that could help us identify such occult disease would improve the initial treatment of patients, particularly in the case of patients with pancreatic cancer in sparing them the morbidity of ineffective aggressive surgery and improving the chance of disease control in such patients. The use of VM110 and near-infrared (NIRF) imaging offers the opportunity to identify occult micrometastatic disease and is the first step in studying molecular processes occurring in cancers in real- time, enabling us to learn more about disease processes, and ultimately better match or develop molecularly targeted personalized treatment for patients with cancer.