Conjugation of monoclonal antibodies with radionuclides.
Radioimmunotherapy, combines specific localization of monoclonal antibody technology, with cytotoxicity of ionizing radiation to deliver selective, cytotoxic treatment.
The monoclonal antibody binds to tumor specific antigens, after which the radionuclide releases ionizing beta particles with a finite radius, causing single, and double stranded DNA breaks to nearby cells, resulting in cellular death.
Targeted activity of the antibody delivers radiation to destroy neoplastic cells at the tumor site, unlike the more diffuse delivery from conventional radiotherapy.
Deposits the greatest energy within the tumor, therefore limiting radiation damage to normal tissues.
Radiolabeled antibodies deliver cytotoxic ionizing radiation to cells.
An ideal combination therapy of biologic and radiolytic mechanisms of action to treat poorly vascularized or bulky tumors, as malignant cells not directly accessible to the monoclonal antibody can still be affected by thr ionizing radiation of the radionuclide.
Utilizes a loer overall dose of radiation , limits whole body exposure to radiation and minmizes toxicity to normal cells and organs.
With 131I-tositumomab (Bexxar) in follicular lymphoma results in a 95% response rate and a 75% complete remission rate, with 77% of complete remission patients remaining free of disease at 5 years.
Yttrium-90 ibritumomab (Zevalin) useful for follicular lymphomas.
As a second line single agent treatment for follicular lymphomas associated with remission rates of 60-80% and complete response rates of 25-40% but most of these refractory or relapsed patients subsequently relapse with a median progression free survival rate of 1 year.