Radiometals as payloads for radioimmunotherapy for lymphoma.
Because of their remarkable effectiveness in radioimmunotherapy (RIT), 2 anti-CD20 monoclonal antibody (MAb) drugs, one labeled with indium 111 for imaging or yttrium 90 for therapy, and another labeled with iodine I 131 for imaging and therapy, have been approved for use in patients with non-Hodgkin's lymphoma (NHL). Successful RIT for lymphomas is due in large part to the rapid and efficient binding of the targeted MAb to lymphoma cells. Carcinomas are more difficult to access, necessitating novel strategies matched with radionuclides with specific physical properties. Because there are many radionuclides from which to choose, a systematic approach is required to select those preferred for a specific application. Thus far, radionuclides with g emissions for imaging and particulate emissions for therapy have been investigated. Radionuclides of iodine were the first to be used for RIT. Many conventionally radioiodinated MAbs are degraded after endocytosis by target cells, releasing radioiodinated peptides and amino acids. In contrast, radiometals have been shown to have residualizing properties, advantageous when the MAb is localized in malignant tissue. b-emitting lanthanides like those of 90Y, lutetium 177, etc. have attractive combinations of biologic, physical, radiochemical, production, economic, and radiation safety characteristics. Other radiometals, such as copper-67 and copper-64, are also of interest. a-emitters, including actinium-225 and bismuth-213, have been used for therapy in selected applications. Evidence for the impact of the radionuclide is provided by data from the randomized pivotal phase III trial of 90Y ibritumomab tiuxetan (Zevalin) in patients with NHL; responses were about 2 times greater in the 90Y ibritumomab tiuxetan arm than in the rituximab arm. It is clear that RIT has emerged as a safe and efficient method for treatment of NHL, especially in specific settings.
DeNardo
Gerald L
GL
Radiodiagnosis and Therapy, Division of Hematology/Oncology, University of California Davis Medical Center, Sacramento, USA. gldenardo@ucdavis.edu
Kennel
Stephen J
SJ
Siegel
Jeffry A
JA
Denardo
Sally J
SJ
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008223:Lymphoma / Q000276:immunology* / Q000532:radiotherapy*; D008670:Metals; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D015019:Yttrium / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D008670:Metals; D015019:Yttrium; C119496:tositumomab I-131