Fluorescent Imaging of Solid Tumors
Primary brain tumors account for 2-3% of all diagnosed cancers each year in the United States and are the sixth leading cause of cancer induced mortality in the adult population. Gliomas, the most common type of malignant brain tumor, are aggressive infiltrative tumors that damage the brain by disruptive local effects. There are no known treatments that are curative for this disease. Diagnosis of grade 4 glioblastoma invariably leads to death with a survival time of less than one year; methods that are palliative or which extend life by several months are considered successful. Many in the medical community believe that patients could realize significant benefit if complete tumor resection could be achieved. This objective remains a daunting challenge because the tumor infiltrates the surrounding normal brain tissue with small tendrilous colonies of neoplastic cells which are extremely difficult to detect; this problem is exacerbated by the constraint that healthy brain tissue cannot be indiscriminately resected at these tumor margins for fear of causing harm or death to the patient.
Because of the obvious importance of the problem, a variety of approaches for improving tumor demarcation are currently being investigated. In light of the great sensitivity possible with fluorescence techniques, there have been surprisingly few reports of the use of endogenous chromophores and exogenous fluorescent agents as tumor margin contrast markers; furthermore, the exogenous dyes that have been investigated for this purpose, with few exceptions, have been developed as photodynamic agents and, as a consequence, have the potential to damage normal brain tissue. With this in mind we participated in a collaborative effort with Dr. Demetrios Nikas and Dr. Peter Black, colleagues at Harvard Medical School (Children's and Brigham and Women's Hospitals), with the goal of developing fluorescent, non-photosensitizing dyes as selective tumor stains to aid the surgeon in the real time demarcation of tumor margins during resection. The successful results of that study using an intracranial glioma in a murine model were recently reported in "Lasers in Surgery and Medicine" 29:11-17 (2001).