Comparative imaging of structure and metabolites in tumours

A novel technique for metabolic imaging using quantitative bioluminescence and single photon imaging was used to measure the distribution of ATP and lactate in two types of human melanoma xenografts with different radiobiologically hypoxic cell fractions (MF: 45 +/- 17% and EE: 6 +/- 3%; mean +/- SD). The tumours were s.c. grown in nude mice and were used for measurement at volumes of 153-3072 mm3. For metabolic imaging the rapidly frozen tumours were serially sectioned, and each cryosection was brought into contact with a frozen bioluminescent enzyme cocktail using a specially designed glass sandwich system. After thawing section and cocktail the luminescence was started, and light was emitted from the section with an intensity that is proportional to the local metabolite concentration. The photons were imaged directly through a microscope and an imaging photon counting system. A clear-cut correlation was documented between the distribution of relatively high ATP concentrations and of viable cell regions. The data obtained showed lower ATP concentrations in the tumour centres compared to the periphery, whereas lactate was inversely distributed within the melanomas. There was a trend towards a decrease in ATP with increasing tumour size in central, but not in peripheral, parts of both melanoma types. The concentration of neither ATP nor lactate measured in corresponding tumour areas showed differences related to the melanoma type. Thus, these two metabolites did not reflect the difference in the radiosensitivity of these tumours.