Identification
- Summary
Technetium Tc-99m tilmanocept is a radiopharmaceutical diagnostic imaging agent indicated with or without scintigraphic imaging for lymphatic mapping and guiding sentinel lymph node biopsy.
- Generic Name
- Technetium Tc-99m tilmanocept
- DrugBank Accession Number
- DB09266
- Background
Technetium Tc-99m tilmanocept is a radiopharmaceutical diagnostic imaging agent approved by the U.S. Food and Drug Administration (FDA) for the imaging of lymph nodes with or without scintigraphic imaging. It is a macromolecule consisting of multiple units of diethylenetriaminepentaacetic acid (DTPA) and mannose, each covalently attached to a 10 kDa dextran backbone Label. DTPA serves as a chelating agent for technetium Tc 99m to bind Label. Technetium Tc-99m tilmanocept is used in lymphatic mapping and lymph node localization in breast cancer, melanoma, clinically node-negative squamous cell carcinoma of the oral cavity, and other solid tumors 2,3. Detecting sentinel lymph node (SLN) is clinically useful in the prognosis and management of the disease, as it is considered as the first lymph node that receives afferent lymphatic drainage from a primary tumor, and may be used to predict tumour staging and metastasis 3. However, as nodal micrometastasis in breast cancer may not be associated with significant changes in survival, it is also important to identify clinically node-negative patients 3.
Technetium Tc-99m tilmanocept is a novel CD206 receptor-targeted molecule that selectively binds to mannose receptors expressed on the surface of reticuloendothelial cells in lymph nodes 1. Due to its relatively small molecular weight and small molecular diameter of 7 nm 1, technetium Tc-99m tilmanocept displays more rapid injection site clearance, high sentinel node extraction, and low distal node accumulation compared to other conventional radiocolloids 3. It achieves high overall accuracy in detecting SLN 2. Once reconstituted and labelled, technetium Tc99m tilmanocept is intended to be injected in close proximity to the tumor being diagnosed and employed in preoperative gamma detection imaging in combination with various other techniques, including scintigraphy, SPECT, and SPECT/CT 4. It may be administered via subcutaneous, intradermal, subareolar, or peritumoral injection, depending on the tutor location and planned injection technique Label. It is marketed under the trade name Lymphoseek. Potential application of technetium Tc-99m tilmanocept to other cancers are being investigated 3.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Synonyms
- Technetium (99mTc) tilmanocept
- Technetium Tc 99m Tilmanocept
- Technetium Tc99 tilmanocept
Pharmacology
- Indication
Indicated with or without scintigraphic imaging for lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a component of intraoperative management Label.
Indicated with or without scintigraphic imaging for guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity, breast cancer or melanoma Label.
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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Technetium Tc 99m tilmanocept binds to the CD206 receptors on the surface of reticuloendothelial cells, such as macrophages and dendritic cells, which are highly expressed in lymph nodes. In clinical studies, technetium Tc 99m tilmanocept has been shown to be detectable in lymph nodes within 10 minutes and up to 30 hours after injection Label. Moreover, Phase 1 clinical studies showed approximately 0.5 to 1.8% of a dose accumulating in draining lymph nodes via specific binding after about 30 minutes. Technetium Tc99m tilmanocept bindng appears to be independent of tumor type or severity 4. It displays rapid injection site clearance, rapid accumulation, long retention in the sentinel node, and low distal node accumulation 3.
- Mechanism of action
The mannose of the molecule acts as a ligand and guides the molecule to selectively bind to human mannose binding receptors (CD206) located on the surface of reticuloendothelial cells residing within lymph nodes, such as macrophages and dendritic cells Label. According to in vitro studies, technetium Tc 99m tilmanocept demonstrates selective binding to CD206 with a primary binding site affinity of Kd = 2.76 x 10^-11 M.
Target Actions Organism AMacrophage mannose receptor 1 ligandHumans - Absorption
In clinical studies, technetium Tc 99m tilmanocept was detectable in lymph nodes within 10 minutes and up to 30 hours after injection. The maximum amount of the accumulated radioactive dose in the liver, kidney, and bladder was reached at 1 hour post-injection and was approximately 1-2% of the total, injected dose in each tissue Label.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Although the metabolism of technetium Tc 99m tilmanocept has not yet been experimentally investigated, tilmanocept may be metabolized in the liver to its main component molecules dextran, mannose and diethylenetriaminepentaacetic acid (DTPA). Subsequently, dextran may be further broken down into glucose. Furthermore, given the predominant role of the liver in the metabolism of technetium Tc 99m tilmanocept, some biliary elimination of the radiopharmaceutical is also expected.4
- Route of elimination
It is believed that technetium Tc 99m tilmanocept is eliminated primarily through the kidneys as primary metabolites. Technetium Tc 99m tilmanocept may undergo hepatic elimination and biliary elimination.4
- Half-life
Technetium Tc99m tilmanocept decays by isomeric transition with a physical half-life of approximately 6 hours. The half-life at the injection site of 1.8 to 3.1 hours Label.
- Clearance
In dose-ranging clinical studies, injection site clearance rates were similar across doses ranging from 4 to 200 mcg with a mean elimination rate constant in the range of 0.222 to 0.396/hr Label.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Tilmanocept was not mutagenic in vitro in the Ames bacterial mutation assay and in the in vitro mouse lymphoma test, and was negative in the in vivo micronucleus test in mice. Studies assessing the carcinogenic potential or effects on reproductive fertility have not been conducted Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol Ambroxol may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. Articaine Articaine may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. Benzocaine Benzocaine may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. Benzyl alcohol Benzyl alcohol may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. Bupivacaine Bupivacaine may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. Capsaicin Capsaicin may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. Chloroprocaine Chloroprocaine may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. Cinchocaine Cinchocaine may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. Cocaine Cocaine may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. Diphenhydramine Diphenhydramine may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Kit for the preparation of Lymphoseek (technetium Tc 99m tilmanocept) Kit 250 ug/1 Intradermal; Subcutaneous Navidea Biopharmaceuticals, Inc. 2016-10-20 2019-06-01 US 
Kit for the preparation of Lymphoseek (technetium Tc 99m tilmanocept) Kit 250 ug/1 Intradermal; Subcutaneous Navidea Biopharmaceuticals, Inc. 2013-03-13 2019-06-01 US Kit for the preparation of Lymphoseek (technetium Tc 99m tilmanocept) Kit 250 ug/1 Intradermal; Subcutaneous Cardinal Health 414, Llc 2017-09-20 Not applicable US Kit for the preparation of Lymphoseek (technetium Tc 99m tilmanocept) Kit 250 ug/1 Intradermal; Subcutaneous Cardinal Health 414, Llc 2017-09-20 Not applicable US
Categories
- ATC Codes
- V09IA09 — Technetium (99mtc) tilmanocept
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 8IHI69PQTC
- CAS number
- 1262984-82-6
- InChI Key
- Not Available
- InChI
- Not Available
- IUPAC Name
- Not Available
- SMILES
- Not Available
References
- General References
- Wallace AM, Han LK, Povoski SP, Deck K, Schneebaum S, Hall NC, Hoh CK, Limmer KK, Krontiras H, Frazier TG, Cox C, Avisar E, Faries M, King DW, Christman L, Vera DR: Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials. Ann Surg Oncol. 2013 Aug;20(8):2590-9. doi: 10.1245/s10434-013-2887-8. Epub 2013 Mar 17. [Article]
- Agrawal A, Civantos FJ, Brumund KT, Chepeha DB, Hall NC, Carroll WR, Smith RB, Zitsch RP, Lee WT, Shnayder Y, Cognetti DM, Pitman KT, King DW, Christman LA, Lai SY: [(99m)Tc]Tilmanocept Accurately Detects Sentinel Lymph Nodes and Predicts Node Pathology Status in Patients with Oral Squamous Cell Carcinoma of the Head and Neck: Results of a Phase III Multi-institutional Trial. Ann Surg Oncol. 2015 Oct;22(11):3708-15. doi: 10.1245/s10434-015-4382-x. Epub 2015 Feb 11. [Article]
- Surasi DS, O'Malley J, Bhambhvani P: 99mTc-Tilmanocept: A Novel Molecular Agent for Lymphatic Mapping and Sentinel Lymph Node Localization. J Nucl Med Technol. 2015 Jun;43(2):87-91. doi: 10.2967/jnmt.115.155960. Epub 2015 May 8. [Article]
- Electronic Medicines Compendium: Lymphoseek (technetium TC 99M tilmanocept) Monograph [Link]
- FDA Approved Drug Products: Lymphoseek (technetium Tc 99m tilmanocept) for injection [Link]
- External Links
- FDA label
- Download (281 KB)
- MSDS
- Download (124 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Diagnostic Breast Cancer 1 3 Completed Diagnostic Breast Cancer / Melanoma 1 3 Completed Treatment Breast Cancer / Melanoma 1 2 Suspended Diagnostic Endometrial Cancer 1 1 Terminated Diagnostic Colorectal Carcinoma (CRC) / Hepatic Metastases 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Kit Intradermal; Subcutaneous 250 ug/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6409990 No 2002-06-25 2020-05-12 US US9439985 No 2016-09-13 2033-09-27 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 100 MSDS - Predicted Properties
- Not Available
- Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Mediates the endocytosis of glycoproteins by macrophages. Binds both sulfated and non-sulfated polysaccharide chains.
- Specific Function
- Mannose binding
- Gene Name
- MRC1
- Uniprot ID
- P22897
- Uniprot Name
- Macrophage mannose receptor 1
- Molecular Weight
- 166010.315 Da
Drug created at October 27, 2015 23:51 / Updated at February 03, 2022 19:50