Dosimetric techniques in 90Y-microsphere therapy of liver cancer: The MIRD equations for dose calculations.

Therapy with 90Y-microspheres is emerging as a mainstream treatment modality in the management of patients with primary and metastatic liver cancer (1,2). The technique involves the administration of 90Y-microspheres into the hepatic artery, which is accessed via the transfemoral route or through a hepatic arterial infusion port or pump. The technique was first introduced by Ariel, who also reported the first series of successful treatment in patients with metastatic colorectal cancer (3,4). The patients were treated with intraarterial chemotherapy and 3.7–5.5 GBq (100–150 mCi) of 90Y-resin microspheres. The estimated radiation dose to the liver from 3.7 GBq (100 mCi) of 90Ymicrospheres was 120–180 Gy using the MIRD approach. It took a few decades since Ariel’s early experience, in the 1960s, to refine the manufacturing technology and administration techniques of 90Y-microspheres before more structured studies could be implemented (5–7). The initial indications, for use in colorectal cancer metastases and hepatocellular carcinoma, have now expanded to include other unresectable metastatic liver tumors (8,9). The development of highly sophisticated techniques of administration has improved the therapeutic efficacy while minimizing the attendant side effects (10). Compared with the growing clinical experience with 90Ymicrosphere therapy, dosimetric data are unsatisfactory largely because of the lack of uniform and well-explained methods. This brief report aims to summarize the principles of 90Y-microsphere dosimetry and provide the mathematic derivations of the equations used in the MIRD schema. Commercially available 90Y-microsphere products include resin microspheres with a specific activity of 40–70 Bq per sphere (SIR-Spheres; Sirtex Medical) and glass microspheres with a specific activity of 2,400–2,700 Bq per sphere (TheraSphere; MDS Nordion), both of which have median diameters of between 35 and 40 mm. Microspheres administered in the hepatic artery are distributed preferentially in the tumor compartment and are trapped within the microvasculature of the tumor. Microspheres are biocompatible but not biodegradable, and therefore no biologic elimination occurs. The entire 90Y dose is delivered over a physical decay period with a half-life of 2.66 d. Radiation delivery from 90Y-microspheres is essentially confined to the liver because of the 3.8-mm mean range and approximately 10-mm maximum range of b-particles in soft tissue. Although, in reality, 90Y-microsphere distribution is never uniform and, in fact, is invariably patchy, with a wide range of variation, MIRD dose estimations are based on the assumption of a uniform distribution. Obviously, this assumption of uniform distribution of the microspheres is acceptable only as a first-order approximation. Despite this recognized limitation, the MIRD methodology provides consistent and reproducible dose estimates.