Fluorodeoxyuridine uptake by human colorectal hepatic metastases after hepatic artery infusion

Tumor response rates after hepatic regional arterial chemotherapy infusion vary from 30% to 83% with little explanation for this variability. Drug clearance by the liver and plasma drug kinetics after arterial infusion have been described, but little is known about actual tumor drug uptake. This study measured fluorodeoxyuridine (FUdR) uptake in colorectal tumors metastatic to the liver and correlated these results with radionuclide flow scans and with tumor response to treatment. In 16 patients with unresectable colorectal hepatic metastases, FUdR (1 microCi/kg) and 99mTc-macroaggregated albumin (MAA) (6 mCi) were injected at a constant rate into the hepatic artery intraoperatively after insertion of a hepatic artery catheter. Liver and tumor biopsy specimens were obtained 2 and 5 minutes after infusion. 3H counts (representing drug uptake) and 99mTc disintegrations (representing blood flow) were measured by scintillation and gamma-counting. The tumor/liver ratios of FUdR and MAA were linearly related (r = 0.73, p less than 0.001). The mean tumor FUdR level was 9.2 +/- 8.9 nmol/gm, and the mean liver FUdR level was 24.5 +/- 16.8 nmol/gm. The mean FUdR tumor/liver ratio was 0.43 +/- 0.36. The extraction of FUdR by tumor was 49%. Thus substantially more drug was taken up by the liver than by the tumor after arterial infusion. There was considerable heterogeneity in FUdR uptake and MAA retention within both tissues. Tumor uptake of drug correlated significantly with MAA retention; higher FUdR levels were seen in tumors that appeared "hot" on radionuclide arterial perfusion scans. Tumor drug uptake was independent of lesion size and percentage of liver involvement.