Correlation between tumour blood flow and fluorouracil distribution in a hypovascular liver metastasis model

The poor response of colorectal liver metastases to fluorinated pyrimidine chemotherapy may be due to poor drug penetration into the tumour. Chemother apy delivered by the blood to well perfused areas of tumour must reach less well perfused areas by diffusion. This study examined the relationship bet ween intratumoural blood flow and drug uptake in a hypovascular liver metas tasis animal model. We used a double isotope technique to examine the micro distribution of the blood flow tracer [I-125]-iodoantipyrine (IAP) and fluo rinated pyrimidine 5-[6-H-3]-fluorouracil (5-FU) within intrahepatic, hypov ascular HSN tumours. There was a significant fall (P < 10(-6)) in both IAP and 5-FU uptake between the liver/tumour edge and tumour centre which resul ted in a significant covariation (P < 10(-5)) in tracer uptake with distanc e. The finding of a close covariation between blood flow and drug uptake in liver metastases suggested that 5-FU diffusion did not compensate for low 5-FU delivery in areas of poor tumour blood flow. The lower 5-FU levels in low compared with high areas of tumour blood flow could reduce the cytotoxi c effect and increase the potential for development of drug resistance.