title: Radiolabelling rituximab with (99m)Tc in three steps procedure.
abstract: Lymphomas are the most frequent haematological malignancy. In non-Hodgkin's lymphomas (NHL), more than 90% of tumor cells express the cluster of differentiation (CD) 20 antigen. At the end of frontline therapy, the evaluation of remission is based on computed tomography (CT) and positron emission tomography coupled with computer tomography (PET/CT) with [(18)F]-fluorodeoxyglucose ([(18)F]FDG). Unfortunately, these techniques are not specific and cannot distinguish residual active tumor from inflammation. The aim of this study was to develop a specific radiotracer of NHL CD 20+ cells for clinical applications. The radiolabelling technique presented, based on the use of tricarbonyl compound, does not include an antibody reduction because this step could damage the protein. Actually, rituximab, an anti-CD 20 chimeric antibody used for the treatment of these NHL, was radiolabelled with Isolink® (99m)Tc-tricarbonyl compound in a three-step procedure without using a specific antibody reducer. Radiolabelling yield was greater than 97%. In vitro experiments showed a conservation of antibody integrity. In vivo experiments using Single-photon emission computed tomography/CT showed significant tumor targeting 24 h after injection of the radiotracer. It was consequently possible to develop an immunoradiolabelling method to specifically detect the residual disease. As this procedure is fast, reproducible and gentle, it will be possible to comply with Good Manufacturing Practices.
authors.affiliation: Radiopharmacy, University Hospital, Toulouse, France.|The Cancer Research Center of Toulouse, Toulouse, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Fontan
authors.affiliation: The Cancer Research Center of Toulouse, Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bezombes
authors.affiliation: UMR 825, INSERM, Toulouse, France.
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Salabert
authors.affiliation: The Cancer Research Center of Toulouse, Toulouse, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Costes
authors.affiliation: UMR 825, INSERM, Toulouse, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Lopez
authors.affiliation: The Cancer Research Center of Toulouse, Toulouse, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournie
authors.affiliation: The Cancer Research Center of Toulouse, Toulouse, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.affiliation: Nuclear medicine, University Hospital, Toulouse, France.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Coulais
authors.affiliation: UMR 825, INSERM, Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Payoux
authors.affiliation: UMR 825, INSERM, Toulouse, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Tafani
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000069283:Rituximab / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D019275:Radiopharmaceuticals; D000069283:Rituximab; D013667:Technetium
keywords: SPECT/CT; immuno imaging; lymphoma; rituximab; tricarbonyl compound