SPIO-MRI in the detection of hepatocellular carcinoma

between 57 and 250nm, and 70%–80% of injected AMI-25 particles are taken up by the liver, 6% by the spleen, and a small amount by the bone marrow.8 Particles larger than 1000nm are more easily taken up by the spleen, while the hepatic uptake of USPIO is smaller and slower than that of SPIO; USPIO stays longer in the blood vessels and more readily accumulates in the lymph nodes and bone marrow.6,7 Organs containing the iron oxide particles show decreased signal intensity on MR imaging, because the particles have high magnetic susceptibility, which has a strong T2* shortening effect. Because the effect of USPIO is weaker than that of SPIO, and the uptake of USPIO by the liver is smaller in amount, a double dose of USPIO is needed to decrease the signal intensity of the liver to the same degree as SPIO does.7 Hepatic parenchyma containing Kupffer cells decreases in signal intensity after the intravenous administration of SPIO, while lesions without Kupffer cells do not show this decrease. Therefore the lesion-liver contrast is enhanced, and the lesions become conspicuous on T2 and T2*-weighted MR imaging in particular. This is the case in most metastatic liver tumors,1,9–11 and the increased lesion conspicuity can be exploited to decrease the threshold size for lesion detection to less than 3mm.11 These contrast agents looked promising in the first stage of clinical use in the United States and European countries, where hepatocellular carcinomas (HCC) are rare relative to metastatic liver tumors. Because SPIO are taken up by Kupffer cells, they reflect the differentiation of hepatocellular tumors to some extent. However, SPIO have not been so striking as far as the detection of HCC is concerned. Although the detection rate of HCC after SPIO administration is better than that with precontrast MR imaging,12–14 it is definitely lower than that of gadolinium (Gd)-enhanced dynamic MRI.14,15 Three basic factors contribute to this light disappointment. First, the decreased signal intensity of cirrhotic liver with SPIO is limited compared Superparamagnetic iron oxides (SPIO) are relatively new contrast agents for magnetic resonance (MR) imaging of the liver. Iron oxide crystal per se is a kind of ferrite and is therefore ferrimagnetic. Ferrimagnetism is the magnetic property that is very similar to ferromagnetism, which is represented by metallic iron, nickel, and cobalt. When crystalline iron oxide is degraded into small particles, the characteristic properties of ferrimagnetism and ferromagnetism, such as spontaneous magnetization, residual magnetization, and magnetic hysterisis are lost, but the high magnetic susceptibility remains in the particles. Thus, these particles are magnetically transformed into a paramagnetic substance. As they retain much higher magnetic susceptibility than usual paramagnetic substances such as ferrous ion (Fe21), ferric ion (Fe31), and gadolinium ion (Gd31), they are called superparamagnetic. Two different classes of iron oxide colloid particles encapsulated by organic material, such as dextran and carboxydextran, are now in clinical use (commercially available) or in clinical trials.1–7 One class of such particles is the SPIO (mean diameter of encapsulated particles, more than 50nm), including AMI-25 (Feridex, Tanabe, Osaka, Japan) and SHU555A (Resovist, Schering, Berlin, Germany) which have a high R2/R1 relaxivity ratio and high T2* shortening effect. The other class is the ultrasmall superparamagnetic iron oxides (USPIO, mean diameter, less than 50nm), including AMI 227, with a lower R2/R1 relaxivity ratio, lower T2* shortening effect and longer half-life in the blood vessels (slower uptake by reticuloendothelial systems [RES]) than the SPIO. These iron oxide colloid particles injected into blood vessels are taken up by the RES, and we can select or target a certain RES by manipulating the size of the particles. Kupffer cells of the liver tend to take up particles with a diameter between 30 and 1000 nm.8 The particle size of AMI-25 is