Transport limits cellular entry of hepatic arterially injected 5-[18F]fluoro-2'-deoxyuridine in human intrahepatic tumors.
The causes of tumor resistance to hepatic arterially infused fluorodeoxyuridine (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 intrahepatic tumors (four with colorectal hepatic metastases, one with hepatoma) were given bolus hepatic arterial (HA) injections of [18F]FdUrd, and their livers imaged dynamically with a dual-detector gamma camera. Cellular entry of [18F]FdUrd was inferred by comparison with HA-injected 99mTc diethylenetriaminepentaacetate, an extracellular indicator. The images were analyzed to determine single-pass, blood-into-cell, extraction fractions [E(FdUrd)] and fractional retention of extracted radiolabel vs. time in tumors and liver. Measured E(FdUrd) ranged from 0.75 to 0.91 (mean 0.87 +/- 0.03) in liver and from 0.56 to 0.96 (mean 0.78 +/- 0.08) in tumors. Fluorine-18 was lost from tumors and liver at similar rates following first-pass throughput of unextracted [18F]FdUrd. Less than 10% of the radiolabel remained in tumor or liver by 3.5 hr, implying that little 18F was incorporated into long-lived 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 transport must be considered in efforts to increase tumor uptake of hepatic arterially infused FdUrd.
Nuclear Medicine Research Laboratory, Memorial Sloan-Kettering Cancer Center.
J R
JR
Bading
E R
ER
Sigurdson
R D
RD
Finn
S D
SD
Yeh
J
J
Ginos
N E
NE
Kemeny
S M
SM
Larson
D000368:Aged; D001692:Biological Transport; D004351:Drug Resistance; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005462:Fluorine Radioisotopes; D006499:Hepatic Artery; D006801:Humans; D007269:Injections, Intra-Arterial; D007424:Intracellular Fluid / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011877:Radionuclide Imaging; D016284:Technetium Tc 99m Pentetate
D005462:Fluorine Radioisotopes; D005467:Floxuridine; D016284:Technetium Tc 99m Pentetate