Technetium-99m-labeled rituximab for use as a specific tracer of sentinel lymph node biopsy: a translational research study

Abstract

PurposeWe aimed to develop and translate a CD20-antigen-targeted radiopharmaceutical, Technetium-99 m-labeled (99mTc) rituximab, for sentinel lymph node (SLN) detection.Methods99mTc-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.ResultsThe 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.Conclusion99mTc-rituximab, specifically binding to CD20, met most of the requirements of an ideal sentinel mapping agent for use in clinical settings.

Retrospective observational study about reducing the false negative rate of the sentinel lymph node biopsy

“…In recent decades, a majority of studies have been devoted for developing novel, consistent SLN tracing methods, to reduce the FNR of SLNB, [ 12 ] resulting in the currently used methods of tracing SLNs: blue dye, [ 13 ] radioisotope, the combination of blue dye and isotope, [ 14 ] fluorescent dye, [ 15 , 16 ] and nanoparticles. [ 17 , 18 ] Though the novel methods of lymphoscintigraphy confer their own unique advantages in reducing the FNR of SLNB in preclinical studies, their application in practice depends upon further prospective clinical studies to identify suitable protocols, and the uptake of such advanced methods might require some time. [ 19 – 21 ]…”

Comparative research on 99mTc-Rituximab and 99mTc-sulfur colloid in sentinel lymph node imaging of breast cancer

“…It is also the target of Rituximab, one of the most effective antitumor monoclonal antibodies developed so far. Xuejuan Wang et al [7] has reported the preparation and use of 99m Tc-Rituximab for SLN detection in animal models and confirmed that it exhibits the desired properties of rapid clearance from the injection site as well as low accumulation in distal nodes. In this work, we carried out a clinical trial to confirm these characteristics in human subjects and to further compare the detection efficiency between 99m Tc-Rituximab and fTcSC.…”