Microspheres for radioembolization of liver malignancies

Abstract

Microsphere radioembolization (RE) is applied increasingly in the management of patients with unresectable liver tumors. This type of internal radiation therapy deploys microspheres, loaded with the high-energy b-emitting radioisotope yttrium-90 (Y, E max = 2.280 MeV [I = 100.0%]), which are injected into the hepatic artery. The normal liver parenchyma is relatively sensitive to ionizing radiation [1]. However, intra-arterial instillation via a catheter results in a preferential accumulation in the tumorous tissue because liver tumors are exclusively supplied by the hepatic artery, by contrast to normal liver tissue that receives its blood supply predominantly from the portal vein [2]. If the radioactive microspheres are of the appropriate size, they will lodge in the tumors’ microvasculature and will subsequently deliver a high-radiation dose to the tumors. Two types of Y-microspheres are currently in clinical use: TheraSphere microspheres (MDS Nordion Inc., Kanata, Ontario, Canada), which have a glass matrix with a diameter of 25 ± 10 μm (mean ± SD), and the SIR-Spheres (SIRTeX Medical Ltd., Sydney, New South Wales, Australia), which are resinbased microspheres and have a diameter of 32 ± 10 μm (mean ± SD). The glass microspheres (Y 2 O 3 –Al 2 O 3 –SiO 2 ) are produced by forming a mixture of yttrium oxide, aluminum oxide and silicon oxide, which is melted at a temperature close to 1500°C. After cooling down, the glass is crushed into particles of a specific size. These particles are then melted again through a flame sprayer. The glass microspheres are obtained by surface tension. Subsequently, the Y glass microspheres are made radioactive by thermal neutron activation in a nuclear reactor [3]. The resin microspheres are produced by tagging Y to preformed Aminex resin (sulfonated divinyl benzene-styrene copolymer) microspheres (Bio-Rad Laboratories, Richmond, CA, USA) through ion exchange reaction. The Y is then precipitated inside the resin by washing with phosphate solutions, yielding insoluble Y-phosphate [4]. Meanwhile, worldwide, over 15,000 Y-RE treatments have been performed using either the resin or the glass microspheres. In the USA, the glass microspheres are approved by the US FDA as a humanitarian device for radiation treatment of unresectable hepatocellular carcinoma (HCC) or as a bridge to surgery or liver transplantation. SIR-Spheres are FDA-approved for the treatment of colorectal cancer metastatic to the liver. In Europe, both microsphere products have a CE marking for the treatment of patients with either primary or metastatic liver cancer. Maarten AD Vente