Lymphoseek

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ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 

 
  



 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Lymphoseek 50 micrograms kit for radiopharmaceutical preparation 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains 50 micrograms of tilmanocept.  
The radionuclide is not part of the kit. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Kit for radiopharmaceutical preparation.   
 
The vial contains a sterile, non-pyrogenic, white to off-white lyophilized powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
This medicinal product is for diagnostic use only. 
 
Radiolabelled Lymphoseek is indicated for imaging and intraoperative detection of sentinel lymph nodes 
draining a primary tumour in adult patients with breast cancer, melanoma, or localised squamous cell 
carcinoma of the oral cavity.   
 
External imaging and intraoperative evaluation may be performed using a gamma detection device. 
   
4.2 Posology and method of administration 
 

This medicinal product is restricted to hospital use only. 
 
The medicinal product should only be administered by trained healthcare professionals with technical 
expertise in performing and interpreting sentinel lymph node mapping procedures.  
 
Posology 
 
The recommended dose is 50 micrograms tilmanocept radiolabelled with technetium Tc 99m at 18.5 MBq 
for same day surgery or 74 MBq for next day surgery.  The dose of 50 micrograms should not be adjusted for 
body weight differences.  The total injection amount should not exceed 50 micrograms tilmanocept, with a 
total maximum radioactivity of 74 MBq per dose.   
 
The recommended minimum time for imaging is 15 minutes post injection. Intraoperative lymphatic 
mapping may begin as early as 15 minutes post injection. 
 
Patients scheduled for surgery on the day of injection will receive 18.5 MBq technetium Tc 99m 
radiolabelled product.  Administration should occur within 15 hours of the scheduled time of the surgery and 
intraoperative detection. 
 



 

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Patients scheduled for surgery on the day after injection will receive 74 MBq technetium Tc 99m 
radiolabelled product.  Administration should occur within 30 hours of the scheduled time of the surgery and 
intraoperative detection.  
 
Special populations 

 
Hepatic or renal impairment  
 

Careful consideration of the activity to be administered in these patients is required since an increased 
radiation exposure is possible.  The radiation dose to the patient would not exceed 2.28 mSv even if none of 
a 74 MBq dose were eliminated. 
 
Extensive dose-range and adjustment studies with the medicinal product in normal and special populations 
have not been performed. The pharmacokinetics of technetium Tc 99m tilmanocept in patients with renal or 
hepatic impairment have not been characterised (see section 5.2). 
 
Elderly population 

 

Elderly patients aged 65 or older (32%) were evaluated in clinical studies; no safety issues were identified.  
No dose adjustment is recommended based on age.  
 
Paediatric population 

 

The safety and efficacy of Lymphoseek in children and adolescents below the age of 18 years has not yet 
been established. No data are available. 
 

Method of administration 
 
This medicinal product must be radiolabelled before administration to the patient.  The radiolabelled product 
is a clear, colourless solution with no visible particles. 
 
Following radiolabelling, administration can be by either intradermal, subcutaneous, intratumoural, or 
peritumoural injection.   
 
For melanoma, administration is intradermal in single or multiple divided injections.  
 
For breast cancer, administration is intradermal, subareolar (single or multiple divided injections) or 
peritumoural (multiple divided injections). 
 
For squamous cell carcinoma of the oral cavity, administration is peritumoural (multiple divided injections). 
 
Each 50 microgram vial contains an additional overfill to ensure that 50 micrograms of tilmanocept can be 
delivered.  However, it is required that the vial be prepared as instructed and a 50 microgram aliquot be used 
for a single patient dose. 
 
Individual injection volumes should not exceed 0.5 mL or be less than 0.1 mL.  Total injection volume 
should be no greater than 1.0 mL and no less than 0.1 mL.  Dilution of the product in volumes greater than 
1.0 mL could affect the in vivo disposition of Lymphoseek. 
 
For instructions for preparation and control of the radiochemical purity of the radiopharmaceutical, see 
section 12. 
 
For patient preparation, see section 4.4. 
 



 

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4.3 Contraindications 
 
Hypersensitivity to the active substance, to any of the excipients listed in section 6.1 or to any of the 
components of the radiolabelled product. 
 
4.4 Special warnings and precautions for use 
 
Potential for hypersensitivity or anaphylactic reactions  
The possibility of hypersensitivity including severe life-threatening fatal anaphylactic / anaphylactoid 
reactions must always be considered. 
 
If hypersensitivity or anaphylactic reactions occur, the administration of the medicinal product must be 
discontinued immediately and intravenous treatment initiated, if necessary. To enable immediate action in 
emergencies, the necessary medicinal products and equipment such as endotracheal tube and ventilator must 
be immediately available. 
 
Individual benefit/risk justification 
For each patient, the radiation exposure must be justifiable by the likely benefit. The activity administered 
should in every case be as low as reasonably achievable to obtain the required diagnostic information. 
 

Renal and hepatic impairment  
Careful consideration of the benefit risk ratio in these patients is required since an increased radiation 
exposure is possible. The estimated radiation dose to the patient would not exceed 2.28 mSv even if none of 
a 74 MBq dose were eliminated (see section 4.2). 
 
Patient preparation  
The patient should be well hydrated before the start of the examination and frequent voiding of urine during 
the initial hours after examination would reduce radiation exposure to the patient.  
 
Specific warnings  
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’. 
 
For precautions with respect to environmental hazard, see section 6.6.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Adding very large volumes of tracing agents or other injectants temporally or anatomically proximal to 
Lymphoseek could affect the in vivo disposition of Lymphoseek.  Additional tracing agents should not be 
injected within 30 minutes of Lymphoseek administration.   
 
No interaction studies have been performed. 
 
4.6 Fertility, pregnancy and lactation 
 

Women of childbearing potential 
When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is 
important to determine whether or not she is pregnant. Any woman who has missed a period should be 
assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has 
missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if 
there are any) should be offered to the patient.  
 
Pregnancy 
There are no data from the use of Lymphoseek in pregnant women.  No reproductive toxicity studies in 
animals were performed, and it is not known if Lymphoseek can cause foetal harm when administered to a 
pregnant woman.  



 

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Radionuclide procedures carried out on pregnant women also involve radiation dose to the foetus. Only 
essential investigations should therefore be carried out during pregnancy, when the likely benefit far exceeds 
the risk incurred by the mother and foetus. 
 
Breast-feeding 
It is not known whether technetium Tc 99m tilmanocept is excreted into human milk.  

Before administering radiopharmaceuticals to a mother who is breast-feeding consideration should be given 
to the possibility of delaying the administration of radionuclide until the mother has ceased breast-feeding, 
and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity 
in breast milk. If administration is considered necessary, breast-feeding should be interrupted for 24 hours 
post injection and the expressed feeds discarded. 

Fertility 
Animal fertility studies have not been conducted with Lymphoseek.  
 
4.7 Effects on ability to drive and use machines 
 
Lymphoseek has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
In clinical trials with 553 patients, the most common adverse reactions were: 
◦ Injection site irritation (0.7%; 4 of 553 patients) 
◦ Injection site pain (0.2%; 1 of 553 patients) 
 
Other adverse reactions were uncommon, and of mild severity and short duration. 
 
Tabulated list of adverse reactions 
 
Clinical studies have evaluated the incidence of adverse reactions listed below in 553 subjects 18 years and 
above who received Lymphoseek. These reactions were temporally related to Lymphoseek administration 
and could be due to other medicinal products administered to patients or surgical procedures. 
 
Adverse reactions observed during clinical studies are listed below by frequency category. Frequency 
categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 
(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000) and not known 
(frequency cannot be estimated from the available data). 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

System Organ Class (SOC) Adverse Drug Reaction (ADR) 
Metabolism and nutrition disorders Uncommon: Hypercalcaemia 
Nervous system disorders Uncommon: Aphasia, Dizziness, Headache, Paraesthesia  
Eye disorders Uncommon: Vision blurred  
Cardiac disorders Uncommon: Sinus tachycardia  
Vascular disorders Uncommon: Flushing  
Gastrointestinal disorders Uncommon: Nausea  
Skin and subcutaneous tissue disorders Uncommon: Skin irritation 
Musculoskeletal and connective tissue 
disorders 

Uncommon: Pain in extremity, Musculoskeletal pain, Neck 
pain, Pain in jaw  

Renal and urinary disorders Uncommon: Micturition urgency, Pollakiuria  



 

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Reproductive system and breast 
disorders 

Uncommon: Breast pain  
 

General disorders and administration 
site conditions 

Uncommon: Injection site irritation, Injection site pain, 
Feeling hot  

Injury, poisoning and procedural 
complications 

Uncommon: Incision site pain, Seroma, Wound dehiscence  

 
Exposure to ionizing radiation is linked with cancer induction and a potential for the development of 
hereditary defects. As the effective dose to an adult (70 kg) is 1.32 mSv when the maximal recommended 
activity of 74 MBq is administered adverse reactions are expected to occur with a low probability. 
  
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows 
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked 
to report any suspected adverse reactions via the national reporting system listed in Appendix V. 
 
4.9 Overdose 
 
The total injection amount should not exceed 50 micrograms tilmanocept, with a total maximum 
radioactivity of 74 MBq per dose.  Chronic or acute overdose is unlikely to occur given the total injection 
amount. 

No clinical consequences were observed at dose levels of 3.7 times the recommended dose of Lymphoseek 
in humans, or at 390 times the anticipated human exposure of tilmanocept in animals. 
 
In the event of administration of a radiation overdose with tilmanocept the absorbed dose to the patient 
should be reduced where possible by increasing the elimination of the radionuclide from the body by 
frequent micturition or by forced diuresis and frequent bladder voiding 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: diagnostic radiopharmaceutical, tumour detection, ATC Code: V09IA09. 
 

Mechanism of action 
Lymphoseek is a receptor-targeted radiopharmaceutical that is designed to rapidly transit lymphatic vessels; 
it biotargets, accumulates, and is retained in primary, key predictive, draining lymph nodes (sentinel lymph 
nodes).  The substance, tilmanocept, specifically binds to mannose binding receptor proteins (CD206) that 
reside on the surface of macrophages and dendritic cells. Macrophages are present in high concentrations in 
lymph nodes. 
 
Tilmanocept is a macromolecule consisting of multiple units of diethylenetriaminepentaacetic acid (DTPA) 
and mannose, each synthetically attached to a 10 kDa dextran backbone.  The mannose acts as a substrate for 
the receptor, and the DTPA serves as a chelating agent for labelling with technetium Tc 99m.  The mean 
diameter of tilmanocept is 7 nm and this small molecular size permits enhanced transit into lymphatic 
channels resulting in rapid and consistent injection site clearance. 
 
Following reconstitution and labelling, Lymphoseek is intended to be injected in close proximity to the 
tumour and used in preoperative gamma detection imaging in conjunction with a stationary gamma camera 
(scintigraphy), single photon emissioncomputed tomography (SPECT), or SPECT/computerized tomography 
SPECT/CT, and/or intraoperatively in conjunction with a gamma detection probe to localise sentinel lymph 
nodes in the lymphatic pathway draining the tumour.  
 



 

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In in vitro studies, technetium Tc 99m tilmanocept exhibited specific and tight binding to human CD206 
receptors with a primary binding site affinity of Kd = 2.76 x x 10-11 M.  In Phase 1 clinical studies, 
approximately 0.5 to 1.8% of the dose is accumulated in draining lymph nodes through specific binding after 
30 minutes.  Technetium Tc 99m tilmanocept binding is independent of tumour type or severity. 
 
Clinical efficacy 
In Phase 3 clinical studies, technetium Tc 99m tilmanocept was detectable in sentinel lymph nodes within 
10 minutes.  In external gamma imaging analysis, bound technetium Tc 99m tilmanocept has been shown to 
be retained in the same draining lymph nodes for up 30 hours.  Preoperative lymphoscintigraphy was 
performed in 100% of melanoma patients, 100% of head and neck squamous cell carcinoma patients, and 
82% of breast cancer patients.  The overall rate of agreement between lymph node localisation (determined 
by radioactivity detection) on preoperative lymphoscintigraphy and intraoperative lymph node survey was 
97.8% for all patients. 
 
In Phase 3 clinical studies in breast cancer patients mapped with both technetium Tc 99m tilmanocept and 
vital blue dye, technetium Tc 99m tilmanocept localised in 99.91% of patients with a mean 2.08 localised 
sentinel lymph nodes per patient by fixed effects meta-analyses.  These rates were significantly greater 
(p<0.0001) against a random effects meta-analysis of localisation rates from published literature for colloidal 
lymphatic mapping agents as used in European clinical practice.  In a fixed effects meta-analysis of two 
Phase 3 studies, technetium Tc 99m tilmanocept localised in 99.99% of the excised lymph nodes stained blue 
by a vital blue dye (concordance).  Alternatively, vital blue dye localised in 66.96% of the excised lymph 
nodes detected by technetium Tc 99m tilmanocept (reverse concordance). 
 
In Phase 3 clinical studies in melanoma patients mapped with both technetium Tc 99m tilmanocept and vital 
blue dye, technetium Tc 99m tilmanocept localised in 99.89% of patients with a mean 2.30 localised sentinel 
lymph nodes per patient by fixed effects meta-analyses.  These rates were significantly greater (p<0.0001) 
against a random effects meta-analysis of localisation rates from published literature for colloidal lymphatic 
mapping agents as used in European clinical practice.  In a fixed effects meta-analysis of two Phase 3 
studies, technetium Tc 99m tilmanocept localised in 99.99% of the excised lymph nodes stained blue by a 
vital blue dye (concordance).  Alternatively, vital blue dye localised in 63.50% of the excised lymph nodes 
detected by technetium Tc 99m tilmanocept (reverse concordance). 
 
In one Phase 3 clinical study in patients with intraoral or cutaneous squamous cell carcinoma, technetium 
Tc 99m tilmanocept localised sentinel lymph nodes in 97.59% of patients who underwent lymph node 
evaluation.  Relative to the pathology status of lymph node collection from a complete lymph node 
dissection, technetium Tc 99m tilmanocept correctly localised in sentinel lymph nodes predictive of 
harbouring metastatic tumour in 38 of 39 patients, for a false negative rate of 2.56%.  The overall accuracy 
of technetium Tc 99m tilmanocept for identification of true positive and true negative patients relative to 
pathology in the localised lymph nodes was 98.80%. 
 
Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Lymphoseek in one or more subsets of the paediatric population for visualisation of lymphatic drainage of 
solid malignant tumours for diagnostic purposes (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties  
 
Two Phase 1 clinical trials in breast cancer patients and one Phase 1 study in melanoma patients have been 
completed. The purpose of the studies included the radiopharmacokinetic evaluation of Lymphoseek. 
 
Distribution 
In one Phase 1 study in breast cancer patients, Lymphoseek at all three doses tested (4, 20, and 
100 micrograms) exhibited fast injection site clearance (elimination rate constants in the range of 0.222/h to 
0.278/h).  Uptake of technetium Tc 99m tilmanocept into the primary sentinel node increased 
dose-dependently (p=0.009): Lymphoseek injection at 4, 20, and 100 micrograms produced primary sentinel 
node levels (LSN) of 0.09 ± 0.20 pmol, 6.53 ± 2.52 pmol, and 10.58 ± 8.43 pmol of technetium Tc 99m 



 

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tilmanocept, respectively.  The percent-of-injected dose reaching the primary sentinel node (%IDSN) was 
0.05% ± 0.10%, 0.52% ± 0.38%, 0.21% ± 0.17% in the 4, 20, and 100 microgram Lymphoseek dose groups, 
respectively.  The plasma %ID per gram for two dose levels peaked at 4 hours; the mean values for the 4 and 
100 microgram doses were 0.0090%/g ± 0.0048%/g and 0.0039%/g ± 0.0046%/g, respectively. The 
20 microgram dose peaked at 2.5 hours with a mean %ID/g of 0.0023%/g ± 0.0005%/g.  
 
In the second Phase 1 study in breast cancer patients in which patients were injected with 20 micrograms 
Lymphoseek, the mean elimination rate constant of technetium Tc 99m tilmanocept was 0.299/h and the 
drug half-life at the injection site was 2.6 h.  The %IDSN was 1.68% ± 1.22% in the 3 hour 
injection-to-surgery group and 1.81% ± 2.19% in the Lymphoseek 16 hour injection-to-surgery group.   
 
In the Phase 1 study in melanoma patients, Lymphoseek at all three doses tested (20, 100, and 
200 micrograms) cleared the injection site with elimination rate constants in the range of 0.227/h to 0.396/h, 
resulting in drug half-life at the injection site of 1.75 to 3.05 h).  Uptake of technetium Tc 99m tilmanocept 
into the primary sentinel node increased dose-dependently: Lymphoseek injection at 20, 100, and 
200 micrograms produced LSN values of 5.01 ± 8.02 pmol, 17.5 ± 13.7 pmol, and 58.2 ± 41.2 pmol of 
technetium Tc 99m tilmanocept, respectively. The %IDSN taken up into the primary lymph node was 0.50% 
for the 20 microgram dose, 0.35% for the 100 microgram dose, 0.58% for the 200 microgram dose of 
Lymphoseek.  The plasma %ID per gram for two dose levels peaked at 15 minutes; the mean values for the 
20 and 200 microgram doses were 0.0104%/g ± 0.0135%/g and 0.0065%/g ± 0.0082%/g, respectively. The 
100 microgram dose peaked at 1 and 2 hours with a mean %ID/g of 0.0018%/g ± 0.001%/g at each 
timepoint.  
 
Elimination 
Technetium Tc 99m tilmanocept is eliminated primarily through the kidneys. The metabolism of technetium 
Tc 99m tilmanocept has not been investigated experimentally. Tilmanocept may be metabolised in the liver 
to its component molecules, namely dextran (which is renally excreted and/or further metabolised to 
glucose), mannose (an endogenous sugar) and diethylenetriaminepentaacetic acid (which is renally excreted). 
As with all general metabolites, especially those in which the liver plays a measurable roll of elimination, 
some biliary elimination of technetium Tc 99m tilmanocept is also likely to occur. 
 
The %ID for liver, kidneys, and bladder as calculated from the whole body scans of breast cancer patients at 
1, 2.5, and 12 hours after administration was below 2.6% at all times (all dose levels combined). The %ID 
for liver, kidneys, and bladder as calculated from the whole body scans of melanoma patients at 1 and 
12 hours after administration ranged from 1.1% to 3.1% at 1 hour, and all decreased to less than 1% by 
12 hours. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, 
acute and repeated dose toxicity, and genotoxicity. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 

Trehalose dihydrate 
Glycine (E640) 
Sodium ascorbate (E301) 
Stannous chloride dihydrate (E512) 
Sodium hydroxide (E524) 
Hydrochloric acid, dilute (E507) 
 
 
6.2 Incompatibilities 



 

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This medicinal product must not be mixed with other medicinal products except those mentioned in section 
6.6 and 12. 
 
6.3 Shelf life 
 
Unopened vial 
18 months. 
 
After radiolabelling 
6 hours.  Do not store above 25°C.  Store using appropriate radiation shielding. 
 
From a microbiological point of view, the product should be used immediately.  If not used immediately, 
in-use storage times and conditions prior to use are the responsibility of the user. 
 
6.4 Special precautions for storage 
 
Do not store above 25°C. 
Store the vial in the outer carton in order to protect from light. 
 
For storage conditions after radiolabelling of the medicinal product, see section 6.3. 
 
Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive materials.  
 
6.5 Nature and contents of container  
 
8 mL type I glass vial with a butyl rubber stopper sealed with a flip-off seal. Each vial contains 
50 micrograms tilmanocept. 
 
Pack-size of 1 and 5 vials. 
 
6.6 Special precautions for disposal and other handling 
 
General warning 
Radiopharmaceuticals should be received, used, and administered only by authorised persons in designated 
clinical settings. Their receipt, storage, use, transfer, and disposal are subject to the regulations and/or 
appropriate licenses of the competent official organisation.  
 
Radiopharmaceuticals should be prepared in a manner which satisfies both radiation safety and 
pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.  
 

Contents of the vial are intended only for use in the preparation and radiolabelling of Lymphoseek and are 
not to be administered directly to the patient without first undergoing the preparative procedure.  Each 50 
microgram vial contains an additional overfill to ensure that 50 micrograms of tilmanocept can be delivered.  
However, it is required that the vial be prepared as instructed and a 50 microgram aliquot be used for a single 
patient dose; any remaining material should be discarded after reconstitution and use, see section 12. 
 
For instructions on reconstitution and radiolabelling of the medicinal product before administration, see 
section 12.  The radiolabelled product is a clear, colourless solution with no visible particles. 
 
If at any time in the preparation of this medicinal product the integrity of this vial is compromised it should 
not be used.  
 
Administration procedures should be carried out in a way to minimise risk of contamination of the medicinal 
product and irradiation of the operators. Adequate shielding is mandatory. 
 
The content of the kit before extemporary preparation is not radioactive. However, after sodium 



 

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pertechnetate (99mTc) is added, adequate shielding of the final preparation must be maintained.  
 
The administration of radiopharmaceuticals creates risks for other persons from external radiation or 
contamination from spill of urine, vomiting, etc. Radiation protection precautions in accordance with 
national regulations must therefore be taken.  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Norgine B.V. 
Antonio Vivaldistraat 150 
1083 HP Amsterdam 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/955/002 
EU/1/14/955/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 19 November 2014 
Date of latest renewal: 16 September 2019 
 
10. DATE OF REVISION OF THE TEXT 
 
 
11. DOSIMETRY 
 
Technetium (99mTc) is produced by means of a (99Mo/99mTc) generator and decays with the emission of 
gamma radiation with a mean energy of 140 keV and a half-life of 6.02 hours to technetium (99mTc) which, in 
view of its long half-life of 2.13 x 105 years can be regarded as quasi stable. 

 
The radiation dose estimation for a number of organs is based on MIRD reference man and MIRD S values, 
and has been calculated from biological data of organ uptake and blood clearance. 
 
The radiation doses to organs and tissues of an average patient (70 kg) per MBq of radiolabelled 
Lymphoseek are shown in Table 1 and Table 2. 

Table 1.  Estimated dose absorbed from Lymphoseek in patients with breast cancera 

Estimated radiation absorbed dose for breast cancer, mGy/MBq 
Target organ Adults 
brain 0.0002 
breast (injection site) 0.0897 
gall bladder wall 0.0019 
lower large intestine wall 0.0007 
small intestine 0.0005 
stomach 0.0010 
upper large intestine wall 0.0007 
kidney 0.0101 



 

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liver 0.0018 
lungs 0.0020 
muscle 0.0005 
ovaries 0.0101 
red marrow 0.0007 
bone 0.0010 
spleen 0.0015 
testes 0.0027 
thymus 0.0063 
thyroid 0.0048 
urinary bladder 0.0032 
total body (blood)b 0.0011 
Effective dose (E)  
(males, mSv/MBq) 0.01600 

Effective dose (E)  
(females, mSv/MBq) 0.01785 

a Calculated from data of 18 breast cancer patients who received four peritumoural injections of 4, 
20, and 100 microgram doses of Lymphoseek. 
b Blood represents total body exposure segregated from independent measurements of other organs 
and tissues. 

 
Table 2.  Estimated dose absorbed from Lymphoseek in patients with melanomaa 

Estimated radiation absorbed dose for melanoma, mGy/MBq 
Target organ Adults with melanoma 
brain 0.0050 
breast (injection site) 0.0427 
gall bladder wall 0.0038 
lower large intestine wall 0.0031 
small intestine 0.0032 
stomach 0.0030 
upper large intestine wall 0.0031 
kidney 0.0150 
liver 0.0050 
lungs 0.0032 
muscle 0.0024 
ovaries 0.0162 
red marrow 0.0027 
bone 0.0047 
spleen 0.0032 
testes 0.0056 
thymus 0.0031 
thyroid 0.0025 
urinary bladder 0.0076 
total body (blood)b 0.0030 
Effective dose (E)  
(males, mSv/MBq) 0.01094 

Effective dose (E)  
(females, mSv/MBq) 0.01357 

a Calculated from data of 18 melanoma patients who received four intradermal injections of 20, 100, 
and 200 microgram doses of Lymphoseek. 
b Blood represents total body exposure segregated from independent measurements of other organs 
and tissues. 

 
 



 

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12. INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS 
 
Radiation safety – Product handling 
Use waterproof gloves, effective radiation shielding, and appropriate safety measures when handling 
Lymphoseek to avoid unnecessary radiation exposure to the patient, occupational workers, clinical 
personnel, and other persons. 
 
Radiopharmaceuticals should be used by or under the control of healthcare professionals who are qualified 
by specific training and experience in the safe use and handling of radionuclides, and whose experience and 
training have been approved by the appropriate governmental agency authorised to license the use of 
radionuclides. 
 
Directions for radiolabelling the tilmanocept powder 50 micrograms vial with technetium Tc 99m 
general considerations 
The vial components of the kit are sterile, non-pyrogenic, and are intended solely for use in the preparation 
of Lymphoseek.  Do not administer the unprepared vial components of the kit directly to a patient. 
Follow aseptic procedures during preparation and administration. 
 
Follow appropriate radiation safety precautions during preparation and administration.  Use radiation 
shielding for radiolabelled Lymphoseek to prevent radiation exposure. 
 
Use only eluate from technetium Tc 99m generator which was previously eluted within 8 hours.  For the 
highest radiochemical purity, reconstitute with freshly eluted technetium Tc 99m generator eluate. 
 
Technetium Tc 99m labelling reactions depend on maintaining the stannous ion in the reduced state.  Sodium 
pertechnetate (Tc 99m) injection containing oxidants should not be used to reconstitute this kit.  Vials are 
sealed under nitrogen; air or oxygen is harmful to the contents of the vial and therefore the vial should not be 
vented. 
 
Lymphoseek, radiolabelled solution for injection should be used within 6 hours after reconstitution.   The 
dose must contain no less than the intended level of Tc 99m radioactivity for same day surgery (18.5 MBq) 
or next day surgery (74 MBq) at the time of administration. 
 
Determination of injection volumes 
Lymphoseek may be administered to a patient as a single injection or as multiple injections.  Prior to 
preparation, determine the planned injection technique and the number of injections that will be used for a 
given patient.  For each injection prepare a separate syringe.  Based on the planned number of injection 
syringes and the planned total injection volume per patient, determine (from Table 3 below) the reconstituted 
vial volume of radiolabelled Lymphoseek. 
 
Each Lymphoseek vial, once reconstituted and radiolabelled, would contain 50 micrograms of product with 
an additional overfill when prepared according to the instructions and administered as noted in Table 3.  The 
overfill is 12.5 micrograms to allow for radiochemical purity testing and to ensure that 50 micrograms of 
tilmanocept can be delivered.  The total contents of the vial should not be administered to a single patient.  
The radiolabelled product is to be used within 6 hours of its preparation.  Discard unused product. 
 



 

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Table 3:  Lymphoseek injections by injection volume 

Desired number of 
injections Total volume to be injected 

Total Lymphoseek vial 
reconstitution volume 

1 x 0.1 mL injection 0.1 mL 0.125 mL 
5 x 0.1 mL injections, or 
2 x 0.25 mL injections, or 
1 x 0.5 mL injection 

0.5 mL 0.625 mL 

5 x 0.2 mL injections, or 
4 x 0.25 mL injections, or 
2 x 0.5 mL injections 

1.0 mL 1.25 mL 

 

Method of preparation  
Preparation of the Lymphoseek radiolabelled solution for injection from the kit is done by the following 
aseptic procedure: 
a. Prior to radiolabelling, inspect the tilmanocept powder vial for any damage.  Do not use if vial integrity 

appears compromised.  
b. For radiolabelling, use sodium pertechnetate (Tc 99m) solution from a technetium Tc 99m generator 

within 8 hours of its elution. 
c. Do not vent the tilmanocept powder vial prior to or during radiolabelling. 
d. Using a sterile syringe, aseptically draw approximately 23.1 MBq or 92.5 MBq of sodium pertechnetate 

(Tc 99m) solution in either about 0.125 mL volume (for 0.125 mL reconstituted vial volume) or about 
0.5 mL volume (for 0.625 mL or 1.25 mL reconstituted vial volume).  Assay the syringe for technetium 
Tc 99m activity in a dose calibrator. 

e. Prior to radiolabelling, write the radioactivity amount, the reconstituted vial volume, date and time, 
expiration time and lot number in the space provided on the radioactive product vial label and affix it to 
the tilmanocept powder vial.  Place the vial in a radiation shield and sanitize the septum with an alcohol 
wipe. 

f. Aseptically add sodium pertechnetate (Tc 99m) solution (from step d above) to the tilmanocept powder 
vial.  Without withdrawing the needle, remove an equal volume of headspace gas.  Do not vent.   

g. Remove the needle, gently swirl the vial to mix the contents, and then let it stand at room temperature for 
at least 15 minutes. 

h. Aseptically add sterile sodium chloride 9 mg/mL (0.9%) solution for injection, if needed, to the 
radiolabelled product in the tilmanocept powder vial to bring the volume to the reconstituted vial volume 
of 0.125 mL, 0.625 mL, or 1.25 mL prior to filling the patient dose in syringe(s).  To normalize pressure, 
withdraw an equal volume of headspace gas. 

i. Assay the radiolabelled vial for total radioactivity using a dose calibrator.  Write the technetium Tc 99m 
activity concentration, total volume, assay time and date, expiration time, and lot number on the shield 
label supplied with the kit.  Affix the label to the shield. 

j. Determine the radiochemical purity of the radiolabelled product as described below.  
k. Withdraw the required volume of the radiolabelled product into the required number of syringes.  Assay 

the syringe(s) in a dose calibrator.  Write the radioactivity amount, date and time of assay, volume, and 
expiration time (this is not to exceed 6 hours from preparation time) on a syringe label and affix it to the 
syringe(s). 

l. Store the radiolabelled product in a shield.  Do not store above 25°C.  Use within the expiry time on the 
label. 

 
Determination of radiochemical purity of radiolabelled Lymphoseek 
Determine radiochemical purity of the radiolabelled Lymphoseek by Instant Thin Layer Chromatography 
(ITLC) using either Whatman Grade 1, 3MM, 31ET Chr or Biodex 150-001 Red Strips (cellulose 
chromatography paper) using the following method: 
 
a. Mark the chromatographic strip for origin, mid and solvent front lines with a pencil as shown below: 
 



 

14 

 

 
 

 Solvent Front 
Line 

 
 

Mid Line 
 
 
 

Origin Line 
 1 cm from 

Bottom  
Whatman Grade 1, 3MM, 
31ET Chromatography strip 

 Biodex 150-001 Red Strips 

 
b. Apply a small drop (3 - 10 microliters) of the radiolabelled product at the center of the origin line 

chromatography strip. 
c. Place the strip into a chromatography chamber containing 1 mL of acetone as the developing solvent.  

Allow the solvent to migrate to the solvent front line (5 cm from the bottom of the Whatman strips and 
3.5 cm for the Biodex strip).  Remove the strip from the chamber, let it dry and cut it in half.  Count each 
half of the strip with a suitable radioactivity counting apparatus (dose calibrator or multichannel 
analyzer). 

d. Calculate the percent radiochemical purity (% RCP) as follows: 
 

% RCP =  
Counts (activity) in bottom half 

  x   100 Counts(activity) in bottom half  + 
Counts(activity) in top half 

 
e. Do not use the radiolabelled Lymphoseek if the radiochemical purity is less than 90%.   

 
Image acquisition/sentinel lymph node mapping 
Breast cancer, melanoma, and squamous cell carcinoma of the oral cavity applications in adults: 
 
• In clinical studies, patients received Lymphoseek up to 30 hours before surgery. A handheld gamma 

counter (represented by any handheld gamma detection probe) was used intraoperatively to identify 
sentinel lymph nodes localising technetium Tc 99m. In clinical studies using Lymphoseek, study 
investigators employed a threshold rule for positive localisation of technetium Tc 99m that was 
estimated using the background radioactivity counts plus three standard deviations from the mean 
background count level (i.e., the three-sigma rule, representing >99.7% probable difference from 
background) [see Table 4]. Background counts were typically determined from tissue at least 
20 centimetres distal to the injection site.  

 
  Table 4:  Example of three-sigma rule threshold 

Background counta Three-sigma threshold value  
5 11.71 
10 19.49 
15 26.62 
20 33.42 
25 40.00 

  a Average of three 2-second counts or one 10-second count 
 

• All lymphatic mapping agents use elements of the lymphatic system for distribution. The imaging and 
detection of sentinel lymph nodes with Lymphoseek is dependent upon its specific molecular targeting 
and binding to reticuloendothelial cells within lymph nodes. Distortion of the underlying lymphatic 



 

15 

system architecture and function by prior extensive surgery, radiation, or metastatic disease may result in 
diminished Lymphoseek localisation in lymph nodes. Based on clinical studies, the rate of localisation 
(percent of all patients with at least one hot node) and degree of localisation (average number of hot 
nodes per patient) of Lymphoseek is not dependent on the radiopharmaceutical injection technique. The 
use of Lymphoseek is intended to complement palpation, visual inspection, and other procedures 
important to lymph node localisation. Intraoperative lymphatic mapping by gamma detection may begin 
as early as 15 minutes post-injection and within 30 hours (for next day surgery) of administration of 
Lymphoseek. 

• After injection of Lymphoseek, external gamma detection imaging may be conducted. Recommended 
time for preoperative imaging is 15 minutes post-injection but may begin as early as 10 minutes.  
Effective preoperative imaging procedures include planar gamma camera scintigraphy, SPECT, and 
SPECT/CT. Although these are complementary to intraoperative gamma probing, such acquired images 
should not be considered a substitute for proficient and thorough intraoperative probing with a handheld 
gamma detection probe.  

 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
 

  



 

16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND 

USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

 



 

17 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer(s) responsible for batch release 
 
GiPharma S.r.l. 
Strada Crescentino snc – 13040 
Saluggia (VC) 
Italia 

 
Norgine B.V. 
Antonio Vivaldistraat 150 
1083 HP Amsterdam 
Netherlands 
 

The printed package leaflet of the medicinal product must state the name and address of the manufacturer 
responsible for the release of the concerned batch. 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION  

• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT 

• Risk management plan (RMP) 
 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and 
interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation and 
any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of an 
important (pharmacovigilance or risk minimisation) milestone being reached.  

 
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same time. 

 
  



 

18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



 

19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 
  



 

20 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer carton 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Lymphoseek 50 micrograms kit for radiopharmaceutical preparation  
tilmanocept 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 

Each vial contains 50 micrograms of tilmanocept. 
 
3. LIST OF EXCIPIENTS 
 
Excipients:  
Trehalose, dihydrate   
Glycine  (E640) 
Sodium ascorbate  (E301) 
Stannous chloride, dihydrate  
Sodium hydroxide  (E524) 
Hydrochloric acid, dilute (E507) 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Kit for radiopharmaceutical preparation 
1 vial 
5 vials  
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Instructions for the reconstitution and radiolabelling of the product are included in this pack.   
For injection after radiolabelling. 
Intradermal, subcutaneous, intratumoural, or peritumoural use after radiolabelling with sodium pertechnetate 
(99mTc). 

 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
  
 
8. EXPIRY DATE 
 
EXP: 
 
The radiolabelled solution can be used for 6 hours when stored below 25°C. 
 
 



 

21 

9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25°C. 
 
Store the vial in the outer carton in order to protect from light. 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Norgine B.V. 
Antonio Vivaldistraat 150 
1083 HP Amsterdam 
Netherlands 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/14/955/002 1 vial 
EU/1/14/955/001  5 vials 
 
13. BATCH NUMBER 
 

Lot:  
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 

 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
Not applicable. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
Not applicable. 
 



 

22 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial label  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Lymphoseek 50 micrograms kit for radiopharmaceutical preparation 
tilmanocept  
 
2. METHOD OF ADMINISTRATION 
 
For injection after radiolabelling with sodium pertechnetate (99mTc). 
 
3. EXPIRY DATE 
 
EXP: 
 
4. BATCH NUMBER 
 
Lot:  
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
Contains an overfill. 
 
Norgine B.V. 
 
 

  



 

23 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Shield label to be applied after radiolabelling  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Lymphoseek 50 micrograms solution for injection 
technetium (99mTc) tilmanocept 
 
Intradermal, subcutaneous, intratumoural, or peritumoural use.  
 
2. METHOD OF ADMINISTRATION 
 
For injection 
 

3. EXPIRY DATE 
 
Use within 6 hours of radiolabelling. 
 
EXP: ________Time/Date 
 
4. BATCH NUMBER 
 
Lot: 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
  
Total activity: ________MBq 
 
Total volume: ________mL 
 
Calibration time: ________Time/Date 
 
 
6. OTHER 
 
Do not store above 25ºC  
 
Contains an overfill. 
 

 
 
 

CAUTION 
RADIOACTIVE 

MATERIAL 

 
 

 
 
  



 

24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



 

25 

Package leaflet: Information for the patient 
 

Lymphoseek 50 micrograms kit for radiopharmaceutical preparation 
tilmanocept 

 
Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you. 
 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your nuclear medicine doctor who will supervise the procedure. 
• If you get any side effects, talk to your nuclear medicine doctor. This includes any possible side effects 

not listed in this leaflet.  See section 4. 
 
What is in this leaflet 
 
1.  What Lymphoseek is and what it is used for 
2.  What you need to know before Lymphoseek is used 
3.  How to use Lymphoseek  
4.  Possible side effects 
5.  How to store Lymphoseek  
6.  Contents of the pack and other information  
 
1. What Lymphoseek is and what it is used for 
 
This medicine is for diagnostic use in adults only. This means that it is used in breast cancer, melanoma or 
oral cavity cancers to help find out about your illness. It is not a treatment for your illness.  
 
Before it is used, the powder in the vial which contains tilmanocept is mixed with a radioactive medicine 
called sodium pertechnetate (containing 99mTc) to make a substance called technetium (99mTc) tilmanocept. 
 
Since technetium (99mTc) tilmanocept contains a small amount of radioactivity it can make parts of the body 
areas visible to doctors during tests to help them see if the cancer has spread to places called ‘lymph nodes’ 
that are found near tumours. The lymph nodes nearest the tumour are called ‘sentinel’ lymph nodes. These 
lymph nodes are where cancer cells are most likely to have spread.  When Lymphoseek has found the 
sentinel lymph nodes, they can be removed and checked to see if there are any cancer cells present.  
Lymphoseek finds the lymph nodes and can be detected using a special camera or detector.  
 
The use of Lymphoseek does involve exposure to small amounts of radioactivity. Your doctor and the 
nuclear medicine doctor have considered that the clinical benefit that you will obtain from the procedure 
with the radiopharmaceutical outweighs the risk due to radiation.   
 
 
2. What you need to know before Lymphoseek is used  
 
Do not use Lymphoseek 
If you are allergic to tilmanocept or any of the other ingredients of this medicine (listed in section 6) or to 
any of the ingredients of the radiolabelled pharmaceutical. 
 
Warnings and precautions 
Talk to your nuclear medicine doctor before you are given Lymphoseek: 
 

• if you have experienced any signs of allergic reaction (listed in section 4) after previous admistration 
of Lymphoseek 

• if you have kidney or liver problems (renal or heptatic disease) 
 
 



 

26 

Children and adolescents  
This medicine is not for use in children and adolescents under 18 years of age because it has not been studied 
in this age group. 
 
Other medicines and Lymphoseek 
Tell your nuclear medicine doctor if you are taking, have recently taken or might take any other medicines. 
This includes medicines obtained without a prescription and herbal medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your 
nuclear medicine doctor for advice before you are given this medicine. 
 
You must inform the nuclear medicine doctor before the administration of Lymphoseek if there is a 
possibility you might be pregnant, if you have missed your period, or if you are breast-feeding.   
When in doubt, it is important to consult your nuclear medicine doctor who will supervise the procedure.  
 
If you are pregnant, the nuclear medicine doctor will only administer this product during pregnancy if a 
benefit is expected which would outweigh the risks.  
 
If you are breast-feeding, breast milk should be discarded for 24 hours after administration of Lymphoseek. 
Please ask your nuclear medicine doctor when you can resume breast-feeding. 
 
Driving and using machines 
It is considered unlikely that Lymphoseek will affect your ability to drive or to use machines.  Your  doctor 
and nuclear medicine doctor will tell you when it is safe to drive after your surgery. 
 
Lymphoseek contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dose. That means it is essentially 
‘sodium-free’. 
 
 
3. How to use Lymphoseek 
 

This medicine is for hospital use only. 
 
There are strict laws on the use, handling and disposal of radiopharmaceutical products.  Lymphoseek will 
only be used in special controlled areas. This product will only be handled and given to you by people who 
are trained to use it safely. These people will take special care for the safe use of this product and will keep 
you informed of their actions.  
 
The nuclear medicine doctor supervising the procedure will decide the quantity of Lymphoseek to be used in 
your case. It will be the smallest quantity necessary to get the desired information.  
 
The quantity to be administered usually recommended for an adult ranges from 18.5 to 74 MBq 
(megabecquerel, the unit used to express radioactivity).  
 
The dose may be divided up into smaller amounts.  This means that the doctor can make more than one 
injection in the area around the tumour. 
 
Before administration of Lymphoseek you should:  
Follow the instructions of your doctor or nuclear medicine doctor. 
 
Administration of Lymphoseek and conduct of the procedure  
Lymphoseek is injected under the skin, under the nipple, or in or around the tumour.  The place depends on 
the type of tumour. 
 



 

27 

Lymphoseek is given either the day before or on the day of your procedure. 
 
Duration of the procedure 
Your nuclear medicine doctor will inform you about the usual duration of the procedure.  
 
The nuclear medicine doctor uses a special camera to find Lymphoseek.  The surgeon uses the pictures taken 
to see where the sentinel lymph nodes are located.  The surgeon will also use a machine that finds the 99mTc 
part of the medicine.  The 99mTc shows the surgeon where the sentinel lymph nodes are located.   
 
When the sentinel lymph node is found, the surgeon removes it.  If there is more than one sentinel lymph 
node, they will remove these nodes as well.  The sentinel lymph nodes are then checked to see if cancer cells 
have spread to them.   
 
What to do after adminstration of Lymphoseek  
The nuclear medicine doctor will inform you if you need to take any special precautions after receiving this 
medicine.  Contact your doctor if you have any questions. 
 
If you have been given more Lymphoseek than you should 
An overdose is unlikely because you will get a specially measured amount of Lymphoseek precisely 
controlled by the doctor supervising the procedure.  However, in the case of an overdose, you will receive 
the appropriate treatment.  
 
If you have any further questions on the use of this medicine, ask the nuclear medicine doctor who 
supervises the procedure.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. The following 
side effects may happen with this medicine: 
 
Uncommon (may affect up to 1 in 100 people): 
• irritation or pain where the injection is given (including the breast and skin) 
• wound pain, wound opening or accumulation of fluid at surgical site 
• feeling sick (nausea) or dizzy  
• blurred vision 
• difficulty speaking 
• headache  
• increased heart rate 
• frequent or urgent need to urinate  
• feeling of warmth, a pricking or tingling sensation, or pain in an extremity, shoulder, the neck or jaw 
• flushing 
• high levels of calcium in the blood 

This radiopharmaceutical will deliver low amounts of ionising radiation associated with the least risk of 
cancer and hereditary abnormalities.  

 
Reporting of side effects  
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in 
this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V.  
By reporting side effects you can help provide more information on the safety of this medicine. 
 
 



 

28 

5. How to store Lymphoseek  
 
You will not have to store this medicine. This medicine is stored under the responsibility of the specialist in 
appropriate premises. Storage of radiopharmaceuticals will be in accordance with national regulation on 
radioactive materials.  
 
The following information is intended for the specialist only.  
 
Do not use this medicine after the expiry date which is stated on the carton and label after “Exp”.  The expiry 
date refers to the last day of that month.  
 
Do not store above 25°C.  Store the vial in the outer carton in order to protect from light. 
 
The radiolabelled solution is stable for 6 hours at a maximum of 25°C. 
 
The radiolabelled product is a clear, colourless solution with no visible particles. Do not use if particulate 
matter and/or discoloration are seen.  
 
Disposal of radiopharmaceuticals should be done in accordance with national regulation on radioactive 
materials. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Lymphoseek contains 
• The active substance is tilmanocept. Each vial contains 50 micrograms of tilmanocept. 
• The other ingredients are trehalose, dihydrate, glycine (E640), sodium ascorbate (E301), stannous 

chloride, dihydrate, sodium hydroxide (E524) and hydrochloric acid, dilute (E507). 
 
What Lymphoseek looks like and contents of the pack 
Before it is used, the powder in the vial is mixed with another medicine called sodium pertechnetate to make 
a substance called technetium (99mTc) tilmanocept. 
 
Pack sizes 
The glass vials are supplied in a carton containing 1 or 5 vials. 
 
 
Marketing Authorisation Holder 
Norgine B.V. 
Antonio Vivaldistraat 150 
1083 HP Amsterdam 
Netherlands 
 
 
Manufacturer 
GiPharma S.r.l. 
Strada Crescentino snc – 13040 
Saluggia (VC) 
Italia 

 
Norgine B.V. 
Antonio Vivaldistraat 150 
1083 HP Amsterdam 
Netherlands 

 



 

29 

This leaflet was last revised in  
 

 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.   
 
----------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
The complete SmPC of Lymphoseek is provided as a tear-off section at the end of the printed leaflet in the 
product package, with the objective to provide healthcare professionals with other additional scientific and 
practical information about the administration and use of this radiopharmaceutical.  
 
Please refer to the SmPC [SmPC should be included in the box]. 
 


	ANNEX I - SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET