To enhance chemotherapeutic efficacy against
cancer, it is important to deliver anticancer drugs preferentially to
cancer cells and to retain the drugs there for a prolonged time. The in vivo prolongation of the exposure time of anticancer drugs in
tumors can be accomplished by decreasing
tumor tissue blood flow (tBF) after anticancer drug administration. The present study demonstrated that
temocapril hydrochloride, an
angiotensin converting enzyme inhibitor, decreases
tumor tBF markedly in LY80
tumor, a subline of
Yoshida sarcoma in the rat, without affecting the blood flow in liver, kidney, bone marrow, and brain. In
tumor areas with flow of above 20 ml/min/100 g, the tBF decreased by approximately 50% due to
temocapril. In
tumor areas with tBF of about 20 ml/min/100 g, it became less than 3 ml/min/100 g with
temocapril and did not recover during the 2 h experiment. These findings were obtained not only in large
tumors, but also in microfoci growing within a transparent chamber. Furthermore, even when
temocapril was administered under the condition of increased
tumor tBF by administering
angiotensin II,
tumor tBF decreased immediately. Using this technique, it should be possible to trap anticancer drugs selectively in
tumor tissue for an extended period of time.