Mapping lymph nodes in cancer management &amp;ndash; role of 99mTc-tilmanocept injection

Tausch, Christoph; Baege, Astrid; Rageth, Christoph

doi:10.2147/ott.s50394

Cited by 23 publications

(15 citation statements)

References 78 publications

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“…Although still debatable, the clinical advantages of SLNB over ALND are apparent, and the procedure is becoming the preferred standard in patients with breast cancer or melanoma 67 . Moreover, SLNB has become established clinical practice in patients with other types of cancer including penile, anal, colorectal and prostate cancer 68 .…”

Section: Lymphatic Mapping Agentsmentioning

confidence: 99%

Lymphatic Imaging: Focus on Imaging Probes

Niu¹,

Chen²

2015

Theranostics

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In view of the importance of sentinel lymph nodes (SLNs) in tumor staging and patient management, sensitive and accurate imaging of SLNs has been intensively explored. Along with the advance of the imaging technology, various contrast agents have been developed for lymphatic imaging. In this review, the lymph node imaging agents were summarized into three groups: tumor targeting agents, lymphatic targeting agents and lymphatic mapping agents. Tumor targeting agents are used to detect metastatic tumor tissue within LNs, lymphatic targeting agents aim to visualize lymphatic vessels and lymphangionesis, while lymphatic mapping agents are mainly for SLN detection during surgery after local administration. Coupled with various signal emitters, these imaging agents work with single or multiple imaging modalities to provide a valuable way to evaluate the location and metastatic status of SLNs.

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Section: Lymphatic Mapping Agentsmentioning

confidence: 99%

Lymphatic Imaging: Focus on Imaging Probes

Niu¹,

Chen²

2015

Theranostics

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“…Although still debatable, the clinical advantages of SLNB over ALND are apparent, and the procedure is becoming the preferred standard in patients with breast cancer or melanoma 31. Moreover, SLNB has become established clinical practice in patients with other types of cancer including penile, anal, colorectal and prostate cancer 32. SLNs can be identified with the help of various lymphatic mapping agents including radiolabeled colloid, blue dyes, and nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

Mapping Sentinel Lymph Node Metastasis by Dual-probe Optical Imaging

Yang¹,

Wang²,

Zhang³

et al. 2017

Theranostics

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Purpose: Sentinel lymph node biopsy (SLNB) has emerged as the preferred standard procedure in patients with breast cancer, melanoma and other types of cancer. Herein, we developed a method to intra-operatively map SLNs and differentiate tumor metastases within SLNs at the same time, with the aim to provide more accurate and real-time intraoperative guidance. Experimental Design: Hyaluronic acid (HA), a ligand of lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, is employed as a SLN mapping agent after being conjugated with a near-infrared fluorophore (Cy5.5). Different sized HAs (5, 10 and 20K) were tested in normal mice and mice with localized inflammation to optimize LN retention time and signal to background ratio. Cetuximab, an antibody against epidermal growth factor receptor (EGFR), and trastuzumab, an antibody against human epidermal growth factor receptor 2 (HER2), were labeled with near-infrared fluorophore (IRDye800) for detecting metastatic tumors. LN metastasis model was developed by hock injection of firefly luciferase engineered human head neck squamous carcinoma cancer UM-SCC-22B cells or human ovarian cancer SKOV-3 cells. The metastases within LNs were confirmed by bioluminescence imaging (BLI). IRDye800-Antibodies were intravenously administered 24 h before local administration of Cy5.5-HA. Optical imaging was then performed to identify nodal metastases. Results: Binding of HA with LYVE-1 was confirmed by ELISA and fluorescence staining. HA with a size of 10K was chosen based on the favorable migration and retention profile. After sequential administration of IRDye800-antibodies intravenously and Cy5.5-HA locally to a mouse model with LN metastases and fluorescence optical imaging, partially metastasized LNs were successfully distinguished from un-metastasized LNs and fully tumor occupied LNs, based on the different signal patterns. Conclusions: Fluorophore conjugated HA is a potential lymphatic mapping agent for SLNB. Dual-tracer imaging with the combination of lymphatic mapping agents and tumor targeting agents can identify tumor metastases within SLNs, thus may provide accurate and real-time intra-operative guidance to spare the time spent waiting for a biopsy result.

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“…This agent has demonstrated faster injection-site clearance than any nonspecific tracer, while retaining equivalent primary SLN uptake. Clinical data have showed an identification rate of 85%–97% and a sensitivity of 90%–100% when SLNB was followed by axillary lymph node dissection [20]. However, to date, 99m Tc-tilmanocept has not been approved by the CFDA, and no clinical trials have been published using this specific tracer in China.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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Mapping lymph nodes in cancer management – role of 99mTc-tilmanocept injection

Cited by 23 publications

References 78 publications

Lymphatic Imaging: Focus on Imaging Probes

Lymphatic Imaging: Focus on Imaging Probes

Mapping Sentinel Lymph Node Metastasis by Dual-probe Optical Imaging

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

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