Abstract
High energy shock waves (HESW) have been reported to be cytotoxic to tumour cells in vitro and in vivo. For that reason they are evaluated as a new modality for cancer treatment. In the present study we have quantified the effect of treatment with multifocal HESW on tumour blood flow and energy status. Blood flow and adenosine triphosphate (ATP) concentration were investigated simultaneously in tumour and adjacent tissue of six treated and six untreated amelanotic hamster melanomas (A-Mel-3) at 3, 12 or 24 h after multifocal application of HESW. 14C-iodoantipyrine autoradiography for blood flow measurements and quantitative ATP imaging bioluminescence were employed. Following treatment, tumour blood flow and ATP concentration were significantly reduced, as compared to control, over the entire period of observation. Three hours after HESW, blood flow and ATP concentration were at the background level. In adjacent tissue, blood flow and ATP concentration were distinctly diminished. We therefore conclude that multifocal HESW induce a breakdown of tumour-, and adjacent tissue perfusion which is accompanied by a significant decrease of intracellular ATP concentration.
Highlights
The purpose of this investigation was to quantify simultaneously the effects of multifocally applied High energy shock waves (HESW) on blood flow and adenosine triphosphate (ATP) concentration in solid tumours, and their adjacent tissue
A wide inter-individual heterogeneity of blood flow and ATP concentration was observed in untreated tumours and untreated adjacent tissue
Untreated tumours and adjacent tissue revealed similar blood flow values of 35.8 ml 100 g-' minm and 34.9 ml 100 g' min', respectively, whereas ATP concentration was higher in adjacent tissue (1.50 mM) than in tumour tissue (1.03 mM)
Summary
Experiments were performed on amelonotic melanoma AMel-3 tumours (Fortner et at., 1961) implanted into the depilated back of male Syrian Golden Hamsters (9-11 weeks old, 80-100 g body weight). Dashed circles indicate the HESW focal region defined by an isobar representing 50% of maximum HESW pressure, which is 5 mm in diameter and 22 mm in the longitudinal axis (Muller, 1990) These equations were fitted by an iterative polynomial regression with a computer program integrated into the image analysis system (IBAS 2.0 Autoradiography Software Package; Kontron GmbH, Eching, Germany). The light intensity of the process was calibrated in absolute terms in mM in relation to tissue volume using tissue-homogenates of known ATP concentrations, as determined by HPLC These standards were processed in the same way as the tumour sections to assess the relationship between concentration level and bioluminescence intensity. Grey levels were measured in four sections of each tumour and adjacent tissue and the ATP concentrations calculated
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