Feridex® and Iron-based Liver AgentsWhatever happened to Feridex® and other iron agents for liver MRI?
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SPIO nanoparticles
In the mid-1990's several iron-based MR contrast agents were designed to undergo uptake into the phagocytic cells of the liver, primarily macrophages (Kupffer cells) and sinusoidal endothelial cells. These agents were colloid suspensions of dextran-coated iron oxide molecules forming single magnetic domains, thus demonstrating superparamagnetism (a property stronger than paramagnetism but not as powerful as ferromagnetism). Because their diameters were measured in nanometers (nm), these agents became known as superparamagnetic iron oxide (SPIO) nanoparticles.
The largest of these nanoparticles (50-100 nm) were found to undergo rapid uptake by the liver. Smaller particles (10-50 nm), often called Ultrasmall SPIOs (US-SPIOs or USPIOs) remained in the blood for many hours and were only slowly phagocytized by the liver. These latter agents continue to excite interest as intravascular and lymphatic contrast agents, discussed further in the next two Q&As.
The largest of these nanoparticles (50-100 nm) were found to undergo rapid uptake by the liver. Smaller particles (10-50 nm), often called Ultrasmall SPIOs (US-SPIOs or USPIOs) remained in the blood for many hours and were only slowly phagocytized by the liver. These latter agents continue to excite interest as intravascular and lymphatic contrast agents, discussed further in the next two Q&As.
T2-weighted image obtained 30 minutes after administration of Ferridex®. Normally functioning liver becomes dark while lesions like this metastasis (arrow) remain bright.
The two most widely marketed SPIO liver agents were Feridex® (Endorem®) and Resovist® (Cliavist®). Although these agents shortened T1, their dominant effect when accumulating in the liver was to preferentially reduce T2 and T2* by bulk susceptibility effects When a T2- or T2*-weighted pulse sequence was performed, normal areas of liver and spleen (that naturally accumulated the contrast agents) showed reduced signal intensity, while tumors, cysts, and other lesions did not change intensity and remained bright.
Notwithstanding initial enthusiasm for these agents, they failed commercially because their diagnostic utility was simply not proved. Although most cancers did not have SPIO uptake, several benign and malignant hepatocellular lesions including focal nodular hyperplasia, hepatic adenoma, hepatocellular carcinoma, and hemangiomas would occasionally accumulate the agents. As a result, by 2012 manufacturers of both agents discontinued global production and sales. Today, Resovist® is available as a liver agent only in Japan.
References
Daldrup-Link HE. Ten things you might not know about iron oxide nanoparticles. Radiology 2017; 284:616-629.
Hori M, Murakami T, Kim T, et al. Detection of hypervascular hepatocellular carcinoma: comparison of SPIO-enhanced MRI with dynamic helical CT. J Comput Assist Tomogr 2002; 26:701-710.
Senéterre E, Taourel P, Bouvier Y, et al. Detection of hepatic metastases: ferumoxides-enhanced MR imaging versus unenhanced MR imaging and CT during arterial portography. Radiology 1996; 200:785-92.
Daldrup-Link HE. Ten things you might not know about iron oxide nanoparticles. Radiology 2017; 284:616-629.
Hori M, Murakami T, Kim T, et al. Detection of hypervascular hepatocellular carcinoma: comparison of SPIO-enhanced MRI with dynamic helical CT. J Comput Assist Tomogr 2002; 26:701-710.
Senéterre E, Taourel P, Bouvier Y, et al. Detection of hepatic metastases: ferumoxides-enhanced MR imaging versus unenhanced MR imaging and CT during arterial portography. Radiology 1996; 200:785-92.