An ongoing challenge in oncology is the identification and elimination of treatment-resistant cells. Hypoxic cells, which are well-studied and treatment-resistant cells, are strongly associated with certain tumors, vascular diseases, and brain tissue regions afflicted by stroke. Diagnosis and treatment of such conditions may be enhanced by developing methods to determine the extent and degree of hypoxia in the affected tissues of individual patients.
The vascular endothelium is ideally situated to respond to changes in local oxygenation and mediate physiological and pathological vascular responses to hypoxia. The oxygenation state of the endothelial cells represents a useful biomarker for tumor growth and metastasis. Tumor vascularization may be an important factor influencing radiotherapy response, and hypoxic vasculature may attenuate the desired effects of therapy as well as stimulate unwanted signaling in disease. Vascular hypoxia is a phenomenon strongly associated with tumor vasculature. Endothelial cells may have a greater resistance to radiation under both aerobic and hypoxic conditions than tumor cells. A need exists for a method of detecting the presence of hypoxic cells associated with a tumor or surrounding vasculature within a patient in a predictable and non-invasive manner. Such a method would provide diagnostic, therapeutic and treatment planning adjuvants for human cancer and other disease states, without the concomitant hazards associated with radioactivity.
Functionalized microbubbles have been developed that contain a selective binding compounds attached to the microbubble surface. The binding compound is designed to selectively bind to a hypoxia-targeting agent attached to the hypoxic cell. The microbubble composition further functions as a targeted contrast agent for the detection of hypoxic cells using imaging methods such as ultrasound, MRI, x-ray scattering, and PET. Each functionalized microbubble can be further functionalized to include at least one therapeutic compound either attached to the surface of the microbubble or contained within it.