Tc-99m tilmanocept and depreotide

Tilmanocept: technetium Tc 99m tilmanocept, Lymphoseek, DTPA-mannosyl-dextran. Depreotide: technetium Tc 99m depreotide, NeoTect, P829. Related Tc-99m somatostatin agent: Tc-99m EDDA/HYNIC-TOC (Tektrotyd)

Oncology & imaging

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Note on this profile. Tilmanocept is an approved prescription radiopharmaceutical used in operating theatres and nuclear-medicine departments. Depreotide was approved in 1999 and later discontinued. There is no community or self-directed use of either.

Summary

Class: Tilmanocept: synthetic dextran-mannose-DTPA conjugate (carbohydrate-based macromolecule, ~7 nm), labelled with technetium-99m. Depreotide: synthetic 10-amino-acid cyclic peptide with a somatostatin-like receptor-binding loop and a built-in Tc-99m-chelating sequence
Mechanism: Tilmanocept's mannose groups bind CD206 (the mannose receptor) on macrophages and dendritic cells inside lymph nodes, so it is retained in the first ("sentinel") nodes draining a tumour. Depreotide binds SSTR2/3/5 on tumour cells, originally to tell malignant from benign lung nodules
Routes studied: Tilmanocept: intradermal, subcutaneous, peritumoural or submucosal injection at the tumour site. Depreotide: intravenous
Half-life: Tc-99m physical half-life 6.0 h. Tilmanocept clears the injection site within minutes and is retained in sentinel nodes for over 30 h. Depreotide blood clearance within hours, renal and hepatobiliary excretion
Storage: Hospital radiopharmacy; kits stored at room temperature and labelled on the day of use †
Regulatory status: Tilmanocept: approved (US 2013, EU 2014, others). Depreotide: approved US 1999, discontinued (around 2010) †

Doses are as reported in studies or by the community — never recommendations.

1What it is

These two agents share only their isotope. Technetium-99m is the workhorse of nuclear medicine: cheap, available from a generator in every department, with a 6-hour and a gamma energy ideal for standard cameras.

Tilmanocept was designed in the late 1990s as a purpose-built sentinel-node tracer. Surgeons removing a melanoma, breast cancer or oral cancer need to know which lymph node the tumour drains to first; if that node is clear the patient can be spared a full node dissection. Older tracers (Tc-99m sulfur colloid, nanocolloid) are inert particles that lodge in nodes by size. Tilmanocept instead carries mannose sugars that bind a receptor on node macrophages, so it leaves the injection site quickly and stays in the first node rather than drifting on to the next. It was approved in the US in 2013 and in the EU in 2014.

Depreotide was a somatostatin analogue built with a technetium-binding sequence inside the peptide itself, so that no separate chelator was needed. Approved in 1999 as NeoTect to help decide whether solitary lung nodules were cancerous, it was overtaken by FDG PET and withdrawn from the market.

2How it's thought to work

Tilmanocept. small size (~7 nm) gives rapid lymphatic uptake from the injection site; multiple mannose groups bind CD206 with high avidity, locking the tracer in the sentinel node for the next day's surgery. A hand-held gamma probe guides the surgeon, often with blue dye as a visual aid. The tracer does not identify cancer in the node; it identifies which node to biopsy.

Depreotide. binds SSTR2, SSTR3 and SSTR5; most non-small-cell lung cancers and many other tumours express these receptors, giving uptake in malignant nodules. False positives occur in granulomatous and inflammatory lesions (sarcoidosis, tuberculosis) that also carry receptors on immune cells.

A mannose-bearing molecule designed to bind the CD206 receptor on macrophages and stay there. Injected at a tumour site it collects in the first draining lymph node and holds, which is what makes sentinel node mapping readable.Schematic — not to scale

3What the research shows

Graded A/B

Tilmanocept sentinel-node detection in melanoma and breast cancer

Two prospective Phase 3 trials (NEO3-05 and NEO3-09) in 154 melanoma and breast cancer patients compared tilmanocept with blue dye in the same patients: tilmanocept detected 99.9% of blue-dye-positive nodes and found additional nodes, including some containing metastases (Sondak 2013, Ann Surg Oncol; Wallace 2013, Ann Surg Oncol). A randomised comparison with Tc-99m sulfur colloid showed similar sentinel-node identification with faster injection-site clearance (Wallace 2003, Ann Surg Oncol pilot; later comparative series). Grading: prospective, within-patient comparator, not blinded. [2][3]

Graded A/B

Head and neck squamous cell carcinoma

A Phase 3 of 83 patients with oral cavity cancer undergoing sentinel-node biopsy followed by complete neck dissection reported a false-negative rate of 2.6% and negative predictive value of 97.8% (Agrawal 2015, Ann Surg Oncol). This underpinned the 2014 label expansion. [4]

Graded B/C

Imaging of macrophage-rich disease (rheumatoid arthritis, atherosclerosis, Kaposi sarcoma)

Pilot studies have used tilmanocept to image CD206-positive macrophages in inflamed joints and vessels; exploratory only.

Graded A/B

Depreotide for solitary pulmonary nodules

A prospective multicentre trial in 114 patients with indeterminate nodules reported sensitivity 96.6% and specificity 73.1% for malignancy (Blum 2000, Chest). Specificity was its weakness; FDG PET offered comparable sensitivity with whole-body staging in one examination, and depreotide fell out of use. [6]

Tc-99m EDDA/HYNIC-TOC (Tektrotyd)

A technetium-labelled octreotide analogue approved in several European countries as a lower-cost SPECT alternative to Ga-68 PET for NETs; prospective series show sensitivity around 80–90% (Gabriel 2003, J Nucl Med; later Polish and Czech series) †. [7]

4Reported side effects and interactions

Literature-reported

Literature (tilmanocept). injection-site pain or irritation (reported in ~1% or fewer in trials), rare hypersensitivity (the label warns of possible reactions and recommends emergency equipment); radiation dose is very low (effective dose well under 1 mSv). No drug interactions established.

Literature (depreotide). adverse reactions in about 1–2%: headache, nausea, dizziness, flushing, fatigue, abdominal pain, transient blood-pressure change; occasional transient changes in blood glucose. Somatostatin analogue therapy would compete for binding.

Community-reported

Community use. essentially none documented for either.

Theoretical. tilmanocept is dextran-based; patients with known dextran allergy are a stated caution †.

Interactions. none clinically significant for tilmanocept. Depreotide: octreotide or lanreotide co-therapy could reduce tumour uptake.

Markers researchers commonly monitor

No blood markers are relevant to a one-off diagnostic injection. Clinically tracked:

Marker	Why it's watched
Sentinel-node histopathology	the result that the tracer exists to obtain; false-negative rate is the key quality metric for a surgical programme.
Number of nodes identified and injection-site to node count ratio	audit measures in sentinel-node biopsy.
For depreotide-era somatostatin imaging: chromogranin A and the hormonal markers relevant to the tumour, as for pentetreotide (#204)

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Not applicable to individuals. Lymphoseek is a kit vial of tilmanocept labelled with sodium pertechnetate Tc-99m in a hospital radiopharmacy; radiochemical purity is checked before the dose is drawn up. NeoTect was a heat-labelled kit (boiled after pertechnetate addition). No calculator link is provided for these compounds.

6Commonly studied alongside

Tc-99m sulfur colloid, nanocolloid and blue dye (the comparators and co-agents in sentinel-node mapping); indocyanine green fluorescence (a newer non-radioactive co-tracer); pentetreotide (#204), DOTATATE (#201) and DOTATOC (#202) as the somatostatin-receptor agents that depreotide competed with.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Lymphoseek FDA-approved March 2013 for lymphatic mapping in breast cancer and melanoma; expanded June 2014 to sentinel-node biopsy in oral cavity squamous cell carcinoma and to broader solid-tumour lymphatic mapping †. NeoTect FDA-approved 1999, no longer marketed
European Union	Lymphoseek EMA-authorised November 2014 for imaging and intraoperative detection of sentinel lymph nodes in adults with breast cancer, melanoma or oral cavity squamous cell carcinoma †. Tektrotyd authorised in several member states (Poland, Czechia, others) †. Depreotide never widely marketed in the EU
United Kingdom	Lymphoseek licensed via MHRA; NHS availability varies †
Australia	Lymphoseek TGA registration †; sentinel-node mapping mostly performed with Tc-99m antimony sulfide colloid
South Africa	Registration status †
Sport (WADA)	Not listed

8Open questions

Whether tilmanocept's receptor-targeted retention translates into fewer false-negative sentinel-node biopsies than colloids in randomised trials; current evidence is comparative but not definitive.
Potential of tilmanocept as a macrophage (CD206) imaging agent in inflammatory and infectious disease, including with PET isotopes (Ga-68 tilmanocept is in early study †).
Whether low-cost Tc-99m somatostatin SPECT (Tektrotyd) retains a role in regions without PET access.

9References

1Vera DR et al. (2001). A synthetic macromolecule for sentinel node detection: 99mTc-DTPA-mannosyl-dextran. J Nucl Med. PubMed
2Sondak VK et al. (2013). Combined analysis of phase III trials evaluating [99mTc]tilmanocept and vital blue dye for identification of sentinel lymph nodes in clinically node-negative cutaneous melanoma. Ann Surg Oncol. PubMed · DOI
3Wallace AM et al. (2013). Comparative evaluation of [99mTc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials. Ann Surg Oncol. PubMed · DOI
4Agrawal A et al. (2015). [99mTc]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. PubMed · DOI
5Azad AK et al. (2015). γ-Tilmanocept, a new radiopharmaceutical tracer for cancer sentinel lymph nodes, binds to the mannose receptor (CD206). J Immunol. PubMed · DOI
6Blum J et al. (2000). Preliminary results of technetium-99m depreotide scintigraphy in the evaluation of solitary pulmonary nodules: a multicenter trial. Chest. PubMed
7Gabriel M et al. (2003). An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors. J Nucl Med. PubMed
8FDA. Lymphoseek (technetium Tc 99m tilmanocept) prescribing information; EMA Lymphoseek EPAR product information. FDA. NeoTect (technetium Tc 99m depreotide) prescribing information (historical). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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11Page history

31 Oct 2026Profile published — awaiting medical review

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