Abstract
Both biodegradable emboli and pharmacological agents can enhance regional therapy for hepatic targeting. Using a rat model with similar haemodynamic characteristics to human colorectal liver tumour and a radio-labelled marker of similar molecular weight to Adriamycin, we have combined the two approaches to see if the effect was addictive. Following induction of liver tumour in male hooded rats by intrahepatic injection of HSN sarcoma cells, the relative distribution of marker, 99mTc methylene diphosphonate (MDP), was studied in three groups given the following by injection into the hepatic artery. (1) Saline (Control) + MDP; (2) Degradable Starch Microspheres (DSM) + MDP; and (3) Angiotensin II + DSM + MDP. Both Degradable Starch Microspheres alone (P less than 0.001) and Degradable Starch Microspheres + Angiotensin II (P = 0.003) significantly increased the retention of marker in liver and tumour at 1 min following injection, with a 12-fold improvement over controls, but the tumour:liver ratio was unaltered. By 90 min the MDP levels in normal hepatic parenchyma had returned to control values. There was relatively less washout with significant retention in tumour tissue in both DSM (P = 0.03) and combination treated animals (P = 0.001), with a significantly improved (P = 0.001) tumour to liver ratio (5.22:1) in combination treated animal relative to those treated with DSM alone.
Highlights
Previous evaluation of the haemodynamic characteristics of this tumour model has shown that its blood supply is derived, as in metastatic colorectal tumours, almost entirely from the hepatic artery, the portal contribution being minimal. These tumours are relatively hypovascular compared to the surrounding normal liver with a tumour: liver hepatic arterial blood flow ratio of 0.6:1 (Hemingway et al, 1990)
The results of this study suggested that the most effective combination was achieved by the slow bolus injection of Angiotensin II, followed 1 min later by degradable starch microspheres (2 mg) and 30 lsl of methylene diphosphonate (MDP) given over 30 s
Whereas there was no significant difference in the tumour:liver ratio at 1 min (P = 0.87) there was a significant difference by 90 min (P = 0.001)
Summary
Liver tumours were induced in male Hooded Lister rats, weight 200-250 g, by a sub capsular injection of 106 HSN sarcoma cells. Previous evaluation of the haemodynamic characteristics of this tumour model has shown that its blood supply is derived, as in metastatic colorectal tumours, almost entirely from the hepatic artery, the portal contribution being minimal. These tumours are relatively hypovascular compared to the surrounding normal liver with a tumour: liver hepatic arterial blood flow ratio of 0.6:1 (Hemingway et al, 1990). The results of this study suggested that the most effective combination was achieved by the slow bolus injection of Angiotensin II, followed 1 min later by degradable starch microspheres (2 mg) and 30 lsl of MDP given over 30 s This schedule was used in the main comparative study
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