title: Synthesis and Preclinical Evaluation of (177)Lu-CHX-A"-DTPA-Rituximab as a Radioimmunotherapeutic Agent for Non-Hodgkin's Lymphoma.
abstract: BACKGROUND
  Radioimmunotherapy is a feasible treatment modality for B-cell lymphomas expressing CD20 antigen. Tagging of anti-CD20 monoclonal antibody with a β(-) emitter will deliver radiation to the tumor preferentially, thereby causing its destruction. This work explores the utility of (177)Lu-CHX-A"-DTPA-Rituximab as a radioimmunotherapeutic agent for non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  Rituximab was conjugated with p-NCS-Bn-CHX-A"-DTPA and radiolabeled with (177)Lu. (177)Lu-CHX-A"-DTPA-Rituximab was characterized by SE-HPLC. In vitro cell binding and inhibition studies were carried out in Raji cells which express CD20 antigen. Biodistribution studies were performed in SCID mice bearing lymphoma at various time intervals.
  
  
  RESULTS
  The CHX-A"-DTPA-Rituximab conjugate prepared had three molecules of DTPA per Rituximab molecule. Radiochemical purity of (177)Lu-CHX-A"-DTPA-Rituximab was >95%. In the HPLC system, (177)Lu-CHX-A"-DTPA-Rituximab showed a single peak (Rt ∼15.5 minutes). In vitro cell binding studies showed 38.9%±1.1% binding of (177)Lu-CHX-A"-DTPA-Rituximab (∼6.7 nM of radioimmunoconjugate) with Raji cells which reduced to 17.7%±0.5% with the addition of 67 nM of cold antibody. Biodistribution studies showed good tumor uptake at all the time points studied.
  
  
  CONCLUSIONS
  In vitro and in vivo studies showed good specificity of (177)Lu-CHX-A"-DTPA-Rituximab toward CD20 antigen. It can be concluded that (177)Lu-CHX-A"-DTPA-Rituximab could be a promising agent in the treatment of NHL.
authors.affiliation: 1 Isotope Production and Applications Division, Bhabha Atomic Research Centre , Mumbai, India .
authors.forename: Mythili
authors.initials: M
authors.lastname: Kameswaran
authors.affiliation: 1 Isotope Production and Applications Division, Bhabha Atomic Research Centre , Mumbai, India .
authors.forename: Usha
authors.initials: U
authors.lastname: Pandey
authors.affiliation: 2 Department of Clinical Pharmacology, ACTREC, Tata Memorial Center , Navi Mumbai, India .
authors.forename: Chetan
authors.initials: C
authors.lastname: Dhakan
authors.affiliation: 2 Department of Clinical Pharmacology, ACTREC, Tata Memorial Center , Navi Mumbai, India .
authors.forename: Kamal
authors.initials: K
authors.lastname: Pathak
authors.affiliation: 2 Department of Clinical Pharmacology, ACTREC, Tata Memorial Center , Navi Mumbai, India .
authors.forename: Vikram
authors.initials: V
authors.lastname: Gota
authors.affiliation: 1 Isotope Production and Applications Division, Bhabha Atomic Research Centre , Mumbai, India .
authors.forename: K V
authors.initials: KV
authors.lastname: Vimalnath
authors.affiliation: 1 Isotope Production and Applications Division, Bhabha Atomic Research Centre , Mumbai, India .
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Dash
authors.affiliation: 1 Isotope Production and Applications Division, Bhabha Atomic Research Centre , Mumbai, India .
authors.forename: Grace
authors.initials: G
authors.lastname: Samuel
mesh_terms: D000818:Animals; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000532:radiotherapy*; D051379:Mice; D016499:Radioimmunotherapy / Q000379:methods*; D000069283:Rituximab / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000069283:Rituximab
keywords: 177Lu; Rituximab (MabThera®); non-Hodgkin's lymphoma; p-NCS-Bn-CHX-A”-DTPA-Rituximab conjugate; radioimmunotherapy