AJR 2001; 177:747-753
Kuszyk Brian S., Corl Frank M., Franano F. Nicholas, Bluemke David A., Hofmann Lawrence V., Fortman Brian J., Fishman Elliot K.
Solid tumors are much more than mere collections of tumor cells. Although tumor cells have specific molecular and genetic targets that are a central focus of current oncology research, the other major componenets of solid tumors—the neovasculature and the interstitium—also have an important impact on tumor detection and treatment. The vasculature and interstitium can limit the delivery of tumor-specific drugs and contrast agents, resulting in striking disparities between results obtained in the laboratory and those obtained in clinical practice. As we enter the age of molecular radiology, the fundamental molecular transport barriers presented by tumors represent a basic and yet often overlooked obstacle.
Jain [1-4] at the Massachusetts General Hospital, Boston, has been a leader in this field, and many of the concepts and experimental results presented in this review are adapted from his work. As Jain has pointed out, potential barriers to systemic drug delivery exist at every step, including transporting the drug via the blood to the targeted tumor, crossing the vessel wall within the tumor, and crossing the tumor interstitium to reach the targeted cells. These barriers to drug delivery apply to all systemic therapies, including conventional chemotherapy, immune mediators, WBC, and even oxygen, which enhances the free-radical-related toxicity of radiation therapy. In this review, we outline the basic composition of solid tumors, describe the process known as angiogenesis by which tumors form abnormal vessels, and briefly discuss the major barriers inherent in solid tumors as a direct result of their composition and abnormal vasculature. Finally, we outline important potential implications of these barriers for imaging and imaging-guided therapy.