Abstract
The regional distribution of blood flow to the LBDS1 fibrosarcoma, transplanted into the subcutaneous site in rats, was investigated using the readily diffusible compound 14C-iodo-antipyrine (14C-IAP). Quantitative autoradiography was used to establish absolute values of specific blood flow F for 100 X 100 X 20 microns adjacent tissue volumes of the unperturbed tumour. Mean blood flow to whole tumours was found to decrease with increase in tumour size. This relationship was abolished if blood flow was only measured in sections cut from the periphery of the tumours. Detailed analysis of a sub-group of tumours showed that blood flow to individual tumours was heterogeneous. The range of blood flow was large, indicating that mean blood flow to a whole tumour is a poor reflection of the blood perfusion pattern of that tumour. Necrotic tumour regions were usually very poorly perfused. With the exception of the smallest tumours studied, blood flow was lower in the centre of tumours than in the periphery. Necrosis also tended to develop centrally. However, the peripheral to central gradient of blood flow was apparent even when densely cellular, viable tumour regions and necrotic regions were analysed separately. The decrease in blood flow with tumour size was also apparent in densely cellular, viable tumour regions when analysed separately. Qualitative comparison of tumour histology and regional blood flow showed that there were areas of very low blood flow associated with viable tumour regions. Less common were areas of rather high blood flow associated with necrotic tumour regions. A complicated relationship exists between tumour histology and blood flow. The quantitative autoradiography technique is suitable for investigating the most poorly perfused and the most well perfused viable fractions of animal tumours which may limit the efficacy of different types of therapy.
Highlights
Larger tumours displayed irregular areas of coagulative necrosis varying in size
(2.3 ± 0.7 x 103 cell nuclei per mm2). These areas could represent the final outcome of focal necrosis locally affecting a majority of cells which have disintegrated and become resorbed
The analysis showed that there was no relationship between blood flow and tumour size in necrotic regions
Summary
A transplanted rat fibrosarcoma, designated LBDSI, was used for these experiments. Details of the origin of this tumour and its maintenance have been given elsewhere (Tozer & Morris, 1989). Maintenance involves subcutaneous transplantation of 1-2 mm tumour pieces into the right flanks of 8-12-week-old male BD9 rats. Tumours between the seventh and fourteenth generations away from the original spontaneous tumour were used for these experiments. Three orthogonal caliper measurements of tumour diameter were used to produce tumour growth curves. Tumour volume (V) was calculated using the formula: V= It/6 (d, x d2x d3)
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