Effect of Vasoactive Drugs on Tumour Blood Flow as Determined by 2H Nuclear Magnetic Resonance Spectroscopy

Abstract

A selective reduction in tumour blood flow (TBF) could enhance the effects of hyperthermia treatment and of drugs toxic to hypoxic cells. Vasodilator-induced changes in TBF were monitored in transplanted rat fibrosarcomas by non-invasively measuring the uptake of D₂O using ²H nuclear magnetic resonance spectroscopy. Hydralazine (1 or 5 mg kg⁻¹) caused a large (45%) reduction in mean arterial blood pressure (MABP) and a 40–60% reduction in TBF. Low-dose hydralazine (0.1 mg kg⁻¹) caused a 20% reduction in MABP but no significant change in TBF. The doses of prazosin (1 mg kg⁻¹) and calcitonin-gene related peptide (CGRP, 1 nmol kg⁻¹) which caused a 20% reduction in MABP led to a 50–60% reduction in TBF. These results demonstrate the advantage of prazosin and CGRP over hydralazine for the reduction of TBF despite a small hypotensive effect. CGRP may be the most suitable of these agents for clinical use because of its short physiological half-life.