Yttrium-90 ibritumomab tiuxetan

Yttrium-90 ibritumomab tiuxetan, also known by the trade name Zevalin (Acrotech Biopharma LLC, USA), is a theranostic radiopharmaceutical approved for the treatment of patients with relapsed or refractory low grade or follicular non-Hodgkin lymphoma (NHL). More specifically, it is a radioimmunotherapy that works by using an antibody, ibritumomab, against the B cell antigen CD20, which is present in more than 90% of NHL tumor cells. The chelate tiuxetan binds the antibody to the beta particle-emitting Yttrium-90 to target and kill cancer cells.     

Characteristics  

• Y-90 half-life of 64.2 hours 

• primarily beta minus decay 

• beta particle mean soft tissue penetration of 5 mm (100-200 cell diameters) with maximum penetration of 11 mm

  • allows for targeted cytotoxic effects with a small range killing nearby tumor cells with variable antigen expression 

• no gamma energy emission 

• SPECT imaging of bremsstrahlung interactions is commonly performed post therapy 

• PET imaging can also be performed using the small amount of internal pair production  

• approximately 7% excreted through urine

Use 

Before treatment, diagnostic imaging (planar/SPECT) may be performed using 5 mCi of indium 111 ibritumomab tiuxetan.  

This treatment regimen is given between 6 and 12 months after the last dose of standard chemotherapy. One dose of non-radiolabeled rituximab is given intravenously. Rituximab binds to CD20 receptors in the blood and spleen, saturating these normal sites of uptake. Premedication with oral acetaminophen and diphenhydramine is recommended. Seven to nine days after this first infusion, an additional dose of Rituximab is administered. Four hours after this dose, Y-90 ibritumomab tiuxetan is then administered intravenously at a dose of 0.4 mCi/kg (14.8 MBq per kg) Y-90 for patients with normal platelet count to a maximum dose of 32 mCi (1184 MBq). A reduced dose of 0.3 mCi/kg (11.1 MBq per kg) Y-90 ibritumomab tiuxetan intravenous infusion should be administered if platelet count is between 100,000 and 150,000/mm³.  

Potential side effects 

• myelosuppression, most often thrombocytopenia

  • contraindicated in patients with ≥25% marrow involvement with lymphoma, impaired bone marrow reserve, and platelet count less than 100,000/mm³

• fatigue 

• nausea, diarrhea 

• nasopharyngitis 

• mucocutaneous reactions 

History and etymology

The phase III First-Line Indolent Trial (FIT) initial results found an increase in median progression-free survival to 37 months with Zevalin treatment compared to 13.5 in controls after first-line induction therapy. A follow up study after 7.3 years reinforced the results with an increase in median progression-free survival of 3 years and a 19% reduction in the risk of relapse at 8 years in patients with advanced follicular lymphoma. 

Ibritumomab tiuxetan as an antibody treatment, as well as conjugated to Indium III and Yttrium 90, were approved by the FDA in February 2002 for the treatment of refractory follicular non-Hodgkin's lymphoma.  

Another FDA approved radioimmunotherapy used to treat non-Hodgkin lymphoma is iodine-131 tositumomab (tradename Bexxar). In the United States, Bexxar has not been produced since February 2014.