[Intraarterial chemotherapy combined with the concept of pharmacoangiogram using noradrenalin]

Abrams predicted that the pharmacoangiogram theory may improve intraarterial chemotherapy. We provide the following evidence to support this hypothesis from an experimental study on Walker-256 xenograft tumors: (1) selective drug delivery to tumor vessels, (2) increased injection pressure, and (3) low tumor blood flow, which are induced by noradrenalin to enhance anti-tumor activity. Walker-256 tumors are divided into 2 groups, hypovascular and hypervascular tumors that arise 2 and 4 days after tumor inoculation, respectively. Noradrenalin mediates anti-tumor activity against hypervascular tumors. The concentrations of Evans blue in Walker-256 tumors are increased in the hypervascular phase and decreased in the hypovascular phase by 4 μg/mL noradrenalin. These data indicate that norepinephrine may decrease capillary circulation, which may increase the blood flow to hypervascular tumor tissues that lack sphincter muscles due to the contraction of precapillary vessels. Mitomycin C concentrations in hypervascular tumors are increased in tumor tissues and decreased in normal tissues. A higher injection pressure than interstitial pressure(20 mmHg) in hypervascular tumors may improve the delivery of antitumor agents to the tumor interstitium and enhance anti-tumor activity. Low blood flow and reperfusion of the tumor due to the contraction reflex of the tumor-feeding artery enhance anti-tumor activity against hypervascular tumors induced by continuous infusion of noradrenalin. Therefore, noradrenalin decreased the tumor tissues blood flow and induced the tumor necrosis.