(99m)Tc(CO)(3)-Ibritumomab tiuxetan; a novel radioimmunoimaging (RII) agent of B cell non-Hodgkin's lymphoma (NHL)

Biol Chem. 2012 Jan;393(1-2):71-5. doi: 10.1515/BC-2011-170.

Abstract

To exploit the B-lymphocyte antigen-CD20 binding capacity of the Ibritumomab tiuxetan (IBTN) monoclonal antibody (mAb) for imaging, the over-expression of B cells in non-Hodgkin's lymphoma (NHL) (a myeloproliferative disorder of the lymphatic system) was investigated. In the current investigation, we present the labeling of the IBTN with technetium-99m ((99m)Tc) through [(99m)Tc(CO)(3)](+) precursor for radioimmunoimaging (RII) of the tumor prior to its treatment with (90)Y labeled IBTN. Labeled IBTN was radiobiologically characterized in terms of radiochemical purity, in vitro stability in human plasma, immunoreactivity, binding with Raji and Ramos cells and biodistribution in a female nude mouse (FNM) model. It was observed that the reduced IBTN (rIBTN) showed more promising radiobiologic characteristics than the nonreduced IBTN. Significantly higher transchelation was seen in excess cysteine compared with histidine. The radioconjugate showed higher saturated binding affinity with CD20 antigen. Significantly higher target (tumor) to background ratios were observed 1 h post-injection (p.i.). Based on radiochemical purity, in vitro stability, immunoreactivity, binding and biodistrubtion in the FNM model, we recommend the radiolabeling of the rIBTN using tricarbonyl technique as a potential RII agent.

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / chemistry
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Monoclonal* / therapeutic use
  • Disease Models, Animal
  • Female
  • Humans
  • Lymphoma, B-Cell / diagnosis*
  • Lymphoma, B-Cell / radiotherapy
  • Mice
  • Mice, Nude
  • Organotechnetium Compounds* / therapeutic use
  • Radiopharmaceuticals* / chemistry
  • Radiopharmaceuticals* / immunology
  • Tissue Distribution
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • technetium 99m tricarbonyl ibritumomab tiuxetan