Rapid in situ cellular kinetics of intracerebral tumor angiogenesis using a monoclonal antibody to bromodeoxyuridine.

The application of a monoclonal antibody to bromodeoxyuridine (BUdR) provides a rapid, reproducible, nontoxic, immunohistochemical method to measure cellular kinetics of intracerebral tumor angiogenesis. The rabbit brain tumor model of angiogenesis consists of tumor and endothelial cell populations with high proliferative rates that demonstrate the close interdependence between microvascular and neoplastic growths as well as topographic gradients, heterogeneity, and regional microdomains of cell proliferation. The labeling index (LI) of endothelial cells was 25.8% at the tumor periphery, compared to 1.7% in the tumor center (P less than 0.001). Concomitant with an increased turnover of neoplastic cells at the tumor periphery. LI was 26.6% with a LI of 7.7% in the center (P less than 0.01). Furthermore, labeled tumor cells tended to be organized around proliferating capillaries, with less DNA synthesis farther from the nearest blood vessel. The established normal microvessels of the brain, e.g., in the opposite tumor-free hemisphere, were mitotically inactive with a LI of less than 0.001%. Quantitation of vascular cytokinetics should be useful in further studies of the pathophysiology of brain tumor angiogenesis and the development of pharmacological approaches directed toward the microvasculature.