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Tumor-selective blood flow decrease induced by an angiotensin converting enzyme inhibitor, temocapril hydrochloride.

K Hori¹, S Saito, H Takahashi

¹Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai. k-hori@idac.tohoku.ac.jp

Japanese Journal of Cancer Research : Gann

|April 13, 2000

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Temocapril hydrochloride, an angiotensin converting enzyme inhibitor, significantly reduces tumor blood flow (tBF) in rats. This targeted reduction in tBF enhances anticancer drug retention within tumors for improved chemotherapy.

Area of Science:

Pharmacology
Oncology
Cardiovascular Physiology

Background:

Enhancing chemotherapeutic efficacy requires preferential drug delivery and prolonged retention in cancer cells.
Reducing tumor tissue blood flow (tBF) post-drug administration is a strategy to increase in vivo drug exposure time in tumors.

Purpose of the Study:

To investigate the effect of temocapril hydrochloride, an angiotensin converting enzyme inhibitor, on tumor tissue blood flow (tBF).
To determine if temocapril hydrochloride can selectively decrease tBF in tumors without impacting normal organ perfusion.

Main Methods:

Administration of temocapril hydrochloride to rats bearing LY80 tumors (Yoshida sarcoma subline).
Measurement of tBF in tumors and normal organs (liver, kidney, bone marrow, brain) using established techniques.

Related Experiment Videos

Assessment of temocapril's effect under conditions of both basal and angiotensin II-induced elevated tumor tBF.

Main Results:

Temocapril hydrochloride markedly decreased tBF in LY80 tumors, with reductions of approximately 50% in high-flow areas and to <3 ml/min/100 g in moderate-flow areas.
Tumor tBF reduction persisted for at least 2 hours and was observed in both large tumors and microscopic tumor foci.
Temocapril effectively reduced tumor tBF even when it was elevated by angiotensin II administration, demonstrating immediate and potent action.

Conclusions:

Temocapril hydrochloride selectively and significantly reduces tumor blood flow in rats.
This reduction in tBF is sustained and effective even under challenging physiological conditions.
Temocapril offers a potential strategy for selectively trapping anticancer drugs in tumor tissue for extended periods, enhancing therapeutic outcomes.