TRANSPORT LIMITS CELLULAR ENTRY OF HEPATIC ARTERIALLY INJECTED 5-[F-18]FLUORO-2'-DEOXYURIDINE IN HUMAN INTRAHEPATIC TUMORS

The causes of tumor resistance to hepatic arterially infused fluorodeo xyuridine (FdUrd) are poorly understood. A previous study showed that sufficient arterial perfusion relative to liver is necessary for tumor response. The present study examined the effect of transport on FdUrd flux from arterial blood into tumor cells. Five patients with large i ntrahepatic tumors (four with colorectal hepatic metastases, one with hepatoma) were given bolus hepatic arterial (HA) injections of [F-18]F dUrd, and their livers imaged dynamically with a dual-detector gamma c amera. Cellular entry of [F-18]FdUrd was inferred by comparison with H A-injected Tc-99m diethylenetriaminepentaacetate, an extracellular ind icator. The images were analyzed to determine single-pass, blood-into- cell, extraction fractions [E(FdUrd)] and fractional retention of extr acted radiolabel vs. time in tumors and liver. Measured E(FdUrd) range d from 0.75 to 0.91 (mean 0.87 +/- 0.03) in river end from 0.56 to 0.9 6 (mean 0.78 +/- 0.08) in tumors. Fluorine-18 was lost from tumors and liver at similar rates following first-pass throughput of unextracted [F-18]FdUrd. Less than 10% of the radiolabel remained in tumor or liv er by 3.5 hr, implying that little F-18 was incorporated into long-liv ed molecular species within tumor or liver. The observations indicate that, in many cases, limited transport significantly reduces the flux of FdUrd into the cells of intrahepatic tumors, implying that transpor t must be considered in efforts to increase tumor uptake of hepatic ar terially infused FdUrd.