Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a “2-day” protocol

Wallace, Anne M.; Hoh, Carl K.; Limmer, Karl K.; Darrah, Denise D.; Schulteis, Gery; Vera, David R.

doi:10.1016/j.nucmedbio.2009.04.007

Cited by 46 publications

(39 citation statements)

References 11 publications

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“…The mean SLN uptake of 99m Tc-tilmanocept was statistically equivalent to that of 99m Tc-SC (P 5 0.213). The extended interval provided by the 2-d protocol demonstrated that SLN accumulation of 99m Tc-tilmanocept can persist for at least 24 h after administration (19). A retrospective analysis of 32 breast cancer patients also found that although the clearance rate of 99m Tc-tilmanocept was faster than that of filtered 99m Tc-SC, there was no significant difference between the 2 radiopharmaceuticals for the detection of radioactive SLNs in 2-d breast lymphatic mapping procedures (20).…”

Section: Preclinical Studiesmentioning

confidence: 99%

99mTc-Tilmanocept: A Novel Molecular Agent for Lymphatic Mapping and Sentinel Lymph Node Localization

Surasi

O’Malley

Bhambhvani

2015

Journal of Nuclear Medicine Technology

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AlabamaCE credit: For CE credit, you can access the test for this article, as well as additional JNMT CE tests, online at https://www.snmmilearningcenter.org. Complete the test online no later than June 2018. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 80% of the questions correctly to receive 1.0 CEH (Continuing Education Hour) credit. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test.Preoperative lymphatic mapping in conjunction with intraoperative γ-probe detection is widely used for sentinel node localization in melanoma, breast cancer, and other malignancies. 99m Tc-radiocolloids have been the standard radiotracers used for sentinel node mapping. 99m Tc-tilmanocept is a receptorbinding molecular imaging agent approved by the U.S. Food and Drug Administration for lymphatic mapping and lymph node localization in breast cancer, melanoma, clinically nodenegative squamous cell carcinoma of the oral cavity, and other solid tumors. It has several advantages over conventional radiocolloids, including rapid injection site clearance, high sentinel node extraction, and low distal node accumulation, which can lead to efficient resource use.

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Section: Preclinical Studiesmentioning

confidence: 99%

99mTc-Tilmanocept: A Novel Molecular Agent for Lymphatic Mapping and Sentinel Lymph Node Localization

Surasi

O’Malley

Bhambhvani

2015

Journal of Nuclear Medicine Technology

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“…Unfortunately, intraoperative injections of radioactive material present logistical and regulatory issues. Conversely, a prolonged interval between tilmanocept administration and SLN mapping is possible due to persistent SLN retention imparted by receptor binding (17). An example would be tilmanocept injection during colonoscopy followed by surgery a week later.…”

Section: Synthesis and Characterization Of Optically Labeled Tilmanoceptmentioning

confidence: 99%

A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging

Emerson¹,

Limmer²,

Hall³

et al. 2012

Radiology

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Purpose:To determine the imaging and receptor-binding properties of a multireporter probe designed for sentinel lymph node (SLN) mapping via nuclear and fluorescence detection. Materials and Methods:The animal experiments were approved by the institutional animal care and use committee. A multireporter probe was synthesized by covalently attaching cyanine 7 (Cy7), a near-infrared cyanine dye, to tilmanocept, a radiopharmaceutical that binds to a receptor specific to recticuloendothelial cells. In vitro binding assays of technetium 99m ( 99m Tc) -labeled Cy7 tilmanocept were conducted at 4°C by using receptor-bearing macrophages. Optical SLN imaging after foot pad administration was performed by using two molar doses of Cy7 tilmanocept. Six mice were injected with 0.11 nmol of 99m Tc-labeled Cy7 tilmanocept (low-dose group); an additional six mice were injected with 31 nmol of 99m Tc-labeled Cy7 tilmanocept (high-dose group) to saturate the receptor sites within the SLN. After 2.5 hours of imaging, the mice were euthanized, and the sentinel and distal lymph nodes were excised and assayed for radioactivity for calculation of SLN percentage of injected dose and extraction. Four mice were used as controls for autofluorescence. Standard optical imaging software was used to plot integrated fluorescence intensity against time for calculation of the SLN uptake rate constant and scaled peak intensity. Significance was calculated by using the Student t test. Results:In vitro binding assays showed subnanomolar affinity (mean dissociation constant, 0.25 nmol/L 6 0.10 [standard deviation]). Fluorescence imaging showed a detection sensitivity of 1.6 310 3 counts ⋅ sec 21 ⋅ mW 21 per picomole of Cy7. All four imaging metrics (percentage of injected dose, SLN extraction, SLN uptake rate constant, and expected peak fluorescence intensity) exhibited higher values (P = .005 to P = .042) in the low-dose group than in the high-dose group; this finding was consistent with receptor-mediated image formation. Conclusion:The multireporter probe

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“…Some of the advantages of the use of γ-tilmanocept include its enhanced specificity and sensitivity for reliable SLN mapping, and its ability to identify unpredictable lymphatic drainage patterns in cancer patients with solid tumors. Many clinical studies, including two complete phase-3 trials for product registration (pending), were performed in cancer patients as well as in animal models on the efficacy and safety of tilmanocept (1,5,6,8–11,13). However, no molecular study has yet been done to elucidate the mechanism of tilmanocept binding to SLN constituents, including the exact binding partner(s) involved (e.g., mannose-binding receptors) of tilmanocept.…”

Section: Discussionmentioning

confidence: 99%

“…Rapid uptake of γ-tilmanocept by SLNs was also observed in as little as 10 min after direct injection into the porcine prostate gland (8). The clinical use of γ-tilmanocept in SLN mapping and biopsy has shown it to be an excellent tool in the staging of a number of solid tumors including melanoma (9,10), breast cancer (9–13), and squamous cell carcinoma (3). …”

Section: Introductionmentioning

confidence: 99%

γ-Tilmanocept, a New Radiopharmaceutical Tracer for Cancer Sentinel Lymph Nodes, Binds to the Mannose Receptor (CD206)

Azad

Rajaram

Metz

et al. 2015

The Journal of Immunology

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γ-tilmanocept (Technetium-99m–labeled- or 99mTc-tilmanocept) is the first mannose-containing, receptor-directed, radiolabeled tracer for the highly sensitive imaging of sentinel lymph nodes (SLNs) in solid tumor staging. To elucidate the mannose-binding receptor that retains tilmanocept in this microenvironment, human macrophages were used which have high expression of the C-type lectin mannose receptor (MR, CD206). Cy3-labeled tilmanocept exhibited high specificity binding to macrophages that was nearly abolished in competitive inhibition experiments. Furthermore, Cy3-tilmanocept binding was markedly reduced on macrophages deficient in the MR by siRNA treatment, and increased on MR-transfected HEK 293 cells. Finally, confocal microscopy revealed co-localization of Cy3-tilmanocept with the macrophage membrane MR and binding of labeled tilmanocept to MR-positive cells [macrophages and/or dendritic cells (DCs)] in human SLN tissues. Together these data provide strong evidence that CD206 is a major binding receptor for γ-tilmanocept. Identification of CD206 as the γ-tilmanocept-binding receptor enables opportunities for designing receptor-targeted advanced imaging agents and therapeutics for cancer and other diseases.

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Sentinel lymph node accumulation of Lymphoseek and Tc-99m-sulfur colloid using a “2-day” protocol

Cited by 46 publications

References 11 publications

99mTc-Tilmanocept: A Novel Molecular Agent for Lymphatic Mapping and Sentinel Lymph Node Localization

99mTc-Tilmanocept: A Novel Molecular Agent for Lymphatic Mapping and Sentinel Lymph Node Localization

A Receptor-targeted Fluorescent Radiopharmaceutical for Multireporter Sentinel Lymph Node Imaging

γ-Tilmanocept, a New Radiopharmaceutical Tracer for Cancer Sentinel Lymph Nodes, Binds to the Mannose Receptor (CD206)

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