The combined measurement of blood flow and metabolism in RIF‐1 tumours in vivo. A study using H₂ flow and ³¹P NMR spectroscopy

Abstract

Blood flow and phosphorus metabolites have been measured simultaneously in the murine RIF-1 tumour in vivo. Blood flow was measured using the H2 washout technique and 31P NMR spectroscopy was used to measure high energy phosphates, inorganic phosphate and intracellular pH within the tumour. Following NMR and flow measurements, hydralazine was administered and the measurements repeated. There was always a decrease in blood flow, and a fall in nucleoside triphosphate detected by NMR, after administration of hydralazine. At blood flows in excess of 15 mL 100 g-1 min-1, the nucleoside triphosphate/inorganic phosphate ratio was 1.0 or greater, whereas at flows in the range of 5-12 mL 100 g-1 min-1 the ratio fell to below 0.5, and at flows below 5 mL 100 g-1 min-1 there was no detectable resonance from nucleoside triphosphate.

31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models

“…This results in a decrease in average cellular oxygen concentrations and the development of hypoxic tissue. A general trend towards lower NTP/Pi with decreasing blood flow has also been reported in the RIF-1 using gaseous wash-out techniques (Lilly et al, 1985;Evelhoch et al, 1986;Bhujwalla et al, 1990b Tumour growth reflects a fine balance between cell division, quiescence, cell death and cell migration (Steel, 1977). This balance may be very different in each of the four tumour lines studied herein, which had different tissues of origin, histological patterns and growth rates.…”

Differences in vascular response between primary and transplanted tumours

“…Also magnetic resonance spectroscopy has been used to demonstrate a reduction in perfusion in transplanted mouse tumours following hydralazine administration as indicated by a reduction in both PCr/Pi and NTP/Pi ratios and a shift to lower pH (Okunieff et al, 1988;Bhujwalla et al, 1990a). Blood flow, assessed by hydrogen clearance is also greatly reduced (Bhujwalla et al, 1990b) whilst there is no detectable change in these parameters in normal muscle.…”

The potential for prazosin and calcitonin gene-related peptide (CGRP) in causing hypoxia in tumours

“…This technique has been used as a non-invasive means of monitoring tumour metabolic status following the administration of vasodilators hydralazine and prostacyclin Bhujwalla et al, 1990a;. Recently a direct relationship between tumour metabolic status and blood flow has been demonstrated (Bhujwalla et al, 1990b). In the present study, we have used 31P MRS to obtain information on tumour blood flow by monitoring changes in tumour metabolism following administration of various vasoactive compounds.…”