title: Development and biological studies of ¹⁷⁷Lu-DOTA-rituximab for the treatment of Non-Hodgkin's lymphoma.
abstract: The optimization of DOTA-NHS-ester conjugation to Rituximab using different Ab:DOTA molar ratios (1:10, 1:20, 1:50 and 1:100) was studied. High radiochemical yield, in vitro stability and immunoreactive fraction were obtained for the Rituximab conjugated at 1:50 molar ratio, resulting in the incorporation of an average number of 4.9 ± 1.1 DOTA per Rituximab molecule. Labeling with 177Lu was performed in high specific activity with great in vitro stability. Biodistribution in healthy and xenographed mice showed tumor uptake and high in vivo stability as evidenced by low uptake in bone. The properties of 177Lu-DOTA-Rituximab prepared from DOTA-NHS-ester suggest the potential for the application of the 177Lu-labeled antibody in preliminary clinical studies.
authors.forename: Adriana V F
authors.initials: AV
authors.lastname: Massicano
authors.forename: Priscilla B
authors.initials: PB
authors.lastname: Pujatti
authors.forename: Lais F
authors.initials: LF
authors.lastname: Alcarde
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Suzuki
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Spencer
authors.affiliation: Radiopharmacy Center and Biotechnology Center - Nuclear and Energy Research Institute - IPEN / CNEN - São Paulo - Brazil and NationalCancerInstitute - INCA - Rio de Janeiro - Brazil. ebaraujo@ipen.br.
authors.forename: Elaine B
authors.initials: EB
authors.lastname: Araújo
mesh_terms: D000818:Animals; D004355:Drug Stability; D006801:Humans; D008187:Lutetium / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008228:Lymphoma, Non-Hodgkin / Q000532:radiotherapy*; D051379:Mice; D016513:Mice, SCID; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000069283:Rituximab / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013388:Succinimides / Q000737:chemistry; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: C502492:DOTA-NHS; D019275:Radiopharmaceuticals; D013388:Succinimides; D000069283:Rituximab; D008187:Lutetium