title: Technetium-99m-labeled rituximab for use as a specific tracer of sentinel lymph node biopsy: a translational research study.
abstract: OBJECTIVE
  We aimed to develop and translate a CD20-antigen-targeted radiopharmaceutical, Technetium-99 m-labeled (99mTc) rituximab, for sentinel lymph node (SLN) detection.
  
  
  METHODS
  99mTc-rituximab was synthesized and tested for stability in human serum. The binding affinity to CD20 was evaluated in Raji cells by flow cytometric analysis. Biodistribution and sentinel node mapping were carried out in bal b/c mice. Eighty-five patients with breast cancer participated in this study. Dynamic sentinel lymphoscintigraphy was first assessed in 12 patients before planar lymphoscintigraphy was assessed in a larger cohort. All patients underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection.
  
  
  RESULTS
  The cell-binding study showed that 99mTc-rituximab possessed compatible affinity to human CD20. In the mechanism study, 99mTc-labeled anti-mouse CD20 monoclonal antibodies could bind to mouse CD20 and accumulate in the SLN with 2.62±1.25 % of the percentage of injected activity, which could be blocked by excessive unlabeled antibody. Low uptake of non-sentinel nodes and fast clearance from the injection site were observed in the mice. Sentinel nodes were identified in 82 of 85 breast cancer patients (96.5%) by lymphoscintigraphy and SLNB. The sensitivity, specificity, and accuracy were 96.8% (30/31), 100% (51/51), and 98.8% (81/82), respectively.
  
  
  CONCLUSIONS
  99mTc-rituximab, specifically binding to CD20, met most of the requirements of an ideal sentinel mapping agent for use in clinical settings.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing Cancer Hospital, Beijing 100142, P. R. China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing Cancer Hospital, Beijing 100142, P. R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing Cancer Hospital, Beijing 100142, P. R. China.
authors.forename: Baohe
authors.initials: B
authors.lastname: Lin
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing Cancer Hospital, Beijing 100142, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing Cancer Hospital, Beijing 100142, P. R. China.
authors.forename: Shizhen
authors.initials: S
authors.lastname: Zhai
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing Cancer Hospital, Beijing 100142, P. R. China.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing Cancer Hospital, Beijing 100142, P. R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing Cancer Hospital, Beijing 100142, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing Cancer Hospital, Beijing 100142, P. R. China.
authors.forename: Xuedi
authors.initials: X
authors.lastname: Han
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, P. R. China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ouyang
mesh_terms: D000328:Adult; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry*; D018951:Antigens, CD20 / Q000737:chemistry*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D061305:Lymphoscintigraphy; D051379:Mice; D008875:Middle Aged; D015609:Organotechnetium Compounds / Q000737:chemistry*; D015203:Reproducibility of Results; D000069283:Rituximab / Q000737:chemistry*; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D014018:Tissue Distribution; D057170:Translational Research, Biomedical; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007074:Immunoglobulin G; D015609:Organotechnetium Compounds; C509712:technetium 99m rituximab; D000069283:Rituximab
keywords: CD20; biopsy; rituximab; sentinel lymph node; specific