Receptor imaging: application to MR imaging of liver cancer.
A new contrast agent for magnetic resonance (MR) imaging, directed to asialoglycoprotein (ASG) receptors on hepatocytes, was used for detection of liver cancer in rats. Ultrasmall superparamagnetic (mean size, 12 nm) particles of iron oxide (USPIOs) were targeted to ASG receptors by coating particles with arabinogalactan (AG). Liver T2 relaxation times decreased more effectively after a single intravenous administration of AG-USPIO than after an equal dose of a conventional superparamagnetic liver MR contrast agent (AMI-25; mean size, 72 nm). Receptor affinity studies demonstrated that receptor-mediated attachment and subsequent cellular endocytosis do not occur in primary malignant (hepatocellular carcinoma) or metastatic (adenocarcinoma) tumors, because the surface ASG receptors are lost during malignant dedifferentiation. In vitro relaxation and in vivo MR imaging experiments of liver tumors show that targeting USPIO to hepatocytes rather than to the mononuclear phagocytic system allows a considerable dose reduction, increases tumor-liver contrast, and potentially allows distinction of ASG-positive (benign hepatocellular) and ASG-negative (malignant hepatocellular) tumors.
Reimer
P
P
Department of Radiology, Massachusetts General Hospital, Charlestown.
Weissleder
R
R
Lee
A S
AS
Wittenberg
J
J
Brady
T J
TJ
D000818:Animals; D037263:Asialoglycoprotein Receptor; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007501:Iron; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D010087:Oxides; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000032:analysis*
D037263:Asialoglycoprotein Receptor; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D011971:Receptors, Immunologic; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide