title: Technetium-99m- or Cy7-Labeled Rituximab as an Imaging Agent for Non-Hodgkin Lymphoma.
abstract: BACKGROUND
  Rituximab was the first monoclonal antibody approved for the treatment of B-cell non-Hodgkin lymphoma (NHL) expressing CD20 antigen. This antibody has also the potential to be used as a specific fluorescent and radiolabel agent for targeting NHL.
  
  
  OBJECTIVE
  To radiolabel rituximab with technetium-99m (99mTc) or Cy7 and evaluate both probes as potential imaging agents for NHL.
  
  
  METHODS
  Rituximab was derivatized with the trifluoroacetyl hydrazino protected form of succinimidyl ester of HYNIC and radiolabeled with 99mTc. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and single-photon emission computed tomography/computed tomography (SPECT/CT) were performed. Raji cells were transfected with luciferase for bioluminescent NHL imaging up to 21 days. Rituximab was labeled with Cy7 for in vivo noninvasive fluorescence imaging up to 96 h.
  
  
  RESULTS
  Radiolabeling was carried out in a fast, reproducible, easy, and stable way with high radiochemical purity and did not interfere with epitope recognition. Biodistribution and SPECT/CT studies showed high liver and discrete tumor uptake. Bioluminescence and fluorescence studies helped us evaluate rituximab-Cy7 in Raji subcutaneous engraftment in BALB/c nude mice.
  
  
  CONCLUSIONS
  Our results support the potential use of rituximab labeled either with 99mTc or Cy7 as a molecular imaging tool for staging, restaging, and guiding surgical excision of tumors, which merits further evaluation.
authors.affiliation: Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
authors.forename: Ximena
authors.initials: X
authors.lastname: Camacho
authors.forename: Camila Longo
authors.initials: CL
authors.lastname: Machado
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: García
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Gambini
authors.forename: Agustina
authors.initials: A
authors.lastname: Banchero
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernández
authors.forename: Natalia
authors.initials: N
authors.lastname: Oddone
authors.forename: Daniela
authors.initials: D
authors.lastname: Bertolini Zanatta
authors.forename: Carolina
authors.initials: C
authors.lastname: Rosal
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Buchpiguel
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.forename: Eloisa
authors.initials: E
authors.lastname: Riva
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000378:metabolism; D002232:Carbocyanines / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D064907:Diagnostic Uses of Chemicals; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging*; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics; D000069283:Rituximab / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D018951:Antigens, CD20; D002232:Carbocyanines; D064907:Diagnostic Uses of Chemicals; D019275:Radiopharmaceuticals; C501744:indotricarbocyanine; D000069283:Rituximab; D013667:Technetium