Temporary blood flow stasis with degradable starch microspheres (DSM) for liver metastases in a rat model

Abstract

A reliable liver metastasis model using intraportal injections of sarcoma cells was established in syngeneic hooded Lister rats to study the blood supply of the tumours and to evaluate the role of degradable starch microspheres (DSM) in conjunction with selective hepatic arterial and portal venous chemotherapy. The tumour/normal liver (T/L) ratio after intra-arterial and intraportal injection of 113Sn microspheres was 1·04 (range: 0·38-1·15) and 0·03 (range: 0·006-0·22), respectively. After intravenous 14C-iodoantipyrine quantitative autoradiography of tumour and normal regions demonstrated a mean T/L ratio of 0·74±0·05. After hepatic artery ligation (HAL) and portal vein ligation (PVL) the values were 0·32±0·05 and 0·42±0·05, respectively. These results confirm that the vascularity of the tumours in this model is similar to human colorectal cancer metastases. Radiolabelled 14C 5-Fluorouracil (5-FU) was given intravenously, via the hepatic artery and via the portal vein (the latter two routes with and without DSM). Quantitative autoradiography of tumour regions showed that selective hepatic arterial administration with DSM resulted in a significantly increased concentration of 14C-5-FU within the tumours. These results suggest that DSM may enhance the therapeutic benefit of hepatic arterial 5-FU by increasing its uptake into tumours.