Nanocis (Technetium-99m Rhenium Sulphide Colloid)
Diagnostic radiopharmaceutical for sentinel lymph node detection and lymphoscintigraphy
Nanocis is a radiopharmaceutical diagnostic agent used in nuclear medicine departments for sentinel lymph node detection, lymphoscintigraphy, and imaging of the reticuloendothelial system. After radiolabelling with technetium-99m, the nanocolloid particles are injected near tumour sites to visualise draining lymph nodes, helping determine whether cancer has spread. Nanocis is prepared and administered exclusively by authorised nuclear medicine specialists in hospital settings.
Quick Facts
Key Takeaways
- Nanocis is a diagnostic radiopharmaceutical used primarily for sentinel lymph node detection in cancer staging, including breast cancer, melanoma, and other solid tumours.
- It is always prepared and administered by nuclear medicine specialists in a hospital setting — patients never self-administer this medication.
- The nanocolloid particles (mean diameter approximately 23–25 nm) are among the smallest available, allowing efficient lymphatic drainage and rapid sentinel node uptake.
- Side effects are very rare but may include allergic reactions; resuscitation equipment must always be immediately available during administration.
- Nanocis is contraindicated in pregnancy due to the ionising radiation exposure to the foetus after radiolabelling with technetium-99m.
What Is Nanocis and What Is It Used For?
Nanocis (NANOCIS 0.24 mg) is a two-vial kit manufactured by CIS bio international, now part of the Curium Group, based in France. When the two vials are mixed and radiolabelled with sodium pertechnetate (99mTc), the resulting preparation is technetium (99mTc) colloidal rhenium sulphide, a radioactive nanocolloid used for scintigraphic imaging in nuclear medicine departments worldwide.
The product belongs to the pharmacotherapeutic group of diagnostic radiopharmaceuticals for the hepatic and reticuloendothelial system (ATC code: V09DB06). Unlike therapeutic radiopharmaceuticals that are designed to destroy cancer cells, Nanocis is purely a diagnostic tool that helps clinicians visualise lymphatic pathways and identify sentinel lymph nodes.
The primary clinical indications for Nanocis, after radiolabelling with technetium-99m, include:
- Sentinel lymph node (SLN) detection: Identification of the first draining lymph node from a tumour site in breast cancer, malignant melanoma, vulvar carcinoma, penile carcinoma, prostate cancer, and head and neck squamous cell carcinoma.
- Lymphoscintigraphy: Visualisation of the regional lymphatic system and lymphatic flow for individualised radiation therapy planning.
- Lymphatic flow assessment: Diagnosis and evaluation of lymphatic oedema (lymphoedema) in the limbs.
- Gastroesophageal scintigraphy: Imaging of the gastrointestinal tract for functional assessment.
- Reticuloendothelial system imaging: When administered intravenously, Nanocis can be used for bone marrow and liver-spleen imaging.
How Does Nanocis Work?
The mechanism of action of Nanocis is based on the physical properties of its nanocolloid particles rather than any pharmacodynamic activity. At the chemical concentrations used for diagnostic examinations, technetium (99mTc) colloidal rhenium sulphide does not exert pharmacological effects on the body.
The key to Nanocis's effectiveness lies in its exceptionally small particle size. Approximately 95% of the particles measure between 8 and 68 nanometres in diameter, with a mean diameter of roughly 23 to 25 nm. This small, uniform particle size is crucial because it determines how efficiently the colloid enters and travels through the lymphatic system.
When injected subcutaneously or intradermally at or near a tumour site, the nanocolloid particles enter the lymphatic capillaries and are transported with lymph fluid to the nearest draining lymph node — the sentinel lymph node. Once they arrive at the node, the particles are phagocytosed (engulfed) by macrophages and retained within the node. The gamma radiation emitted by technetium-99m (140 keV photons, physical half-life of 6.02 hours) then allows the sentinel node to be visualised using a gamma camera or detected intraoperatively with a handheld gamma probe.
When Nanocis is administered intravenously (for liver-spleen or bone marrow imaging), the colloidal particles are rapidly cleared from the bloodstream by the reticuloendothelial system (RES) with a plasma half-life of approximately 2.5 minutes. The distribution is typically 80–90% to Kupffer cells in the liver, 5–10% to the spleen, and the remainder to bone marrow, enabling imaging of these organs.
What Should You Know Before Receiving Nanocis?
Because Nanocis is a radiopharmaceutical that involves exposure to ionising radiation, several important safety considerations must be addressed before its use. The nuclear medicine physician responsible for the procedure must carefully weigh the potential diagnostic benefit against the radiation risk for each individual patient. This benefit-risk assessment is a fundamental principle of radiation protection in medicine.
Contraindications
Nanocis is contraindicated in the following situations:
- Hypersensitivity: Known allergy to rhenium sulphide (the active substance), gelatine, or any of the other excipients contained in the product.
- Pregnancy: Confirmed or suspected pregnancy, as nuclear medicine procedures deliver a radiation dose to the foetus. Any woman of childbearing potential must have pregnancy excluded before administration.
Warnings and Precautions
Several important precautions apply to the use of Nanocis:
- Allergic reactions: There is a possibility of hypersensitivity or anaphylactic reactions with any radiopharmaceutical. Equipment for emergency resuscitation, including corticosteroids, antihistamines, and epinephrine (adrenaline), must be immediately available during and after administration.
- Radiation safety: Appropriate aseptic technique and radiation safety precautions must be maintained throughout preparation, administration, and disposal. All personnel involved must follow institutional and national regulations for handling radioactive materials.
- Paediatric use: The product should be used with caution in patients under 18 years of age. The indication must be carefully considered, and paediatric doses should be calculated according to body weight or body surface area using established guidelines such as those from the European Association of Nuclear Medicine (EANM).
- Hydration: Adequate hydration before and after the procedure should be ensured. Patients should be encouraged to void frequently to reduce radiation exposure to the bladder.
- Quality control: The radiolabelled preparation must undergo quality control testing before use. Radiochemical purity must be at least 95% before administration to patients.
Pregnancy and Breastfeeding
Pregnancy: Nanocis is strictly contraindicated in pregnant women or women who may be pregnant. Nuclear medicine procedures performed during pregnancy deliver a radiation dose to the foetus, which carries potential risks including teratogenic effects and increased lifetime cancer risk. When a radiopharmaceutical must be administered to a woman of childbearing potential, pregnancy must be ruled out with appropriate testing. Any woman who has missed a period should be assumed to be pregnant until proven otherwise.
Breastfeeding: Before administering Nanocis to a breastfeeding mother, the nuclear medicine physician must assess whether the investigation can reasonably be delayed until breastfeeding has ceased. If administration during breastfeeding is judged to be necessary, breastfeeding should be interrupted and the expressed milk discarded. The nuclear medicine physician will advise the mother on when breastfeeding can safely be resumed, based on the specific activity administered and the decay characteristics of technetium-99m (half-life 6.02 hours). Generally, a period of approximately 12 to 24 hours is recommended, though this may vary depending on the dose administered.
Fertility: No specific studies on the effects of Nanocis on fertility have been conducted. As with all procedures involving ionising radiation, the radiation dose to the gonads should be kept as low as reasonably achievable (ALARA principle).
How Does Nanocis Interact with Other Drugs?
Unlike many conventional pharmaceutical agents, Nanocis has not been associated with significant drug-drug interactions through formal interaction studies. This is largely because the product acts through a purely physical mechanism (particle transport and phagocytosis) rather than through pharmacological pathways that could be affected by other medications.
Nevertheless, several categories of drugs and procedures deserve consideration because they may influence the biodistribution of the nanocolloid or affect the quality of imaging results:
Factors That May Affect Lymphoscintigraphy Results
| Factor | Potential Effect | Clinical Significance |
|---|---|---|
| Prior surgery at injection site | Disrupted lymphatic drainage pathways | May alter sentinel node identification |
| Prior radiation therapy | Lymphatic fibrosis and altered drainage | May reduce uptake in irradiated nodes |
| Corticosteroids (systemic) | Altered macrophage function | Potential minor effect on phagocytic uptake |
| Chemotherapy agents | Altered lymph node architecture | May affect node detection sensitivity |
| Local anaesthetics at injection site | Altered local blood flow and lymphatic drainage | Generally considered acceptable for clinical use |
Important Considerations
Patients should inform their nuclear medicine physician of all medications they are currently taking, including prescription drugs, over-the-counter medicines, and herbal supplements, before undergoing any nuclear medicine procedure. While no formal contraindicated drug interactions exist for Nanocis, a comprehensive medication review helps the clinical team optimise the imaging protocol and interpret results accurately.
It is also important to note that the technetium-99m used for radiolabelling may interact with certain medications that affect technetium biodistribution. For example, patients who have recently received other technetium-99m-labelled agents should have an appropriate interval between procedures to avoid interference.
Additionally, procedures such as sentinel lymph node biopsy are frequently performed in conjunction with injection of a vital blue dye (such as patent blue V or isosulfan blue). The combined use of Nanocis and blue dye is well established in clinical practice and is not considered an adverse drug interaction. Rather, the dual-tracer technique enhances the detection rate of sentinel lymph nodes compared to either method alone.
What Is the Correct Dosage of Nanocis?
Nanocis is never self-administered by patients. The preparation, quality control, and administration of this radiopharmaceutical are performed exclusively by authorised nuclear medicine specialists in dedicated facilities equipped with appropriate radiation safety measures. The dosage is expressed in megabecquerels (MBq), a unit of radioactivity, rather than in milligrams of the drug substance.
The preparation process involves reconstituting the kit (combining Vials A and B) with sodium pertechnetate (99mTc) solution, followed by heating at 100°C for 30 minutes. The resulting radiolabelled colloid must achieve a radiochemical purity of at least 95% before it can be administered to patients.
Adults
| Indication | Dose (MBq) | Route | Notes |
|---|---|---|---|
| SLN detection – Breast cancer | 7.4–37 MBq | Subcutaneous (peritumoral/periareolar) | Higher dose for 2-day protocols to compensate for Tc-99m decay |
| SLN detection – Melanoma | 10–100 MBq (typically 20–40 MBq) | Intradermal (4+ depots around tumour) | Volume ≤0.2 mL per injection site |
| SLN detection – Other cancers | 10–100 MBq | Perilesional (subcutaneous/intradermal) | Adjusted per institutional protocol |
| Lymphatic flow scintigraphy | 20–80 MBq per limb | Subcutaneous (distal extremity) | Both limbs may be injected for comparison |
| Bone marrow imaging | 200–400 MBq | Intravenous | For visualising reticuloendothelial system distribution |
Children and Adolescents
The use of Nanocis in patients under 18 years of age should be carefully considered, and the indication must be justified given the radiation exposure involved. Paediatric doses are calculated as a fraction of the adult dose based on body weight or body surface area, following the EANM (European Association of Nuclear Medicine) paediatric dosage guidelines.
Paediatric Dosage Guidance
- Liver/spleen imaging: 0.56–2.78 MBq per kilogram body weight, administered intravenously
- Bone marrow imaging: 1.11–5.55 MBq per kilogram body weight, administered intravenously
- Minimum activity: 18.5 MBq (to ensure adequate image quality regardless of body weight)
Elderly Patients
No specific dose adjustment is required for elderly patients. Standard adult doses apply. However, as with all patients, the nuclear medicine physician will consider the individual's renal function, overall health status, and the balance between diagnostic benefit and radiation exposure when determining the appropriate dose.
Missed Dose
The concept of a missed dose does not apply to Nanocis in the conventional sense, as it is a single-administration diagnostic agent given in a clinical setting. If a scheduled nuclear medicine procedure is postponed or cancelled, the prepared radiolabelled product cannot be stored for later use beyond 6 hours from preparation due to the decay of technetium-99m. A new preparation would be required for a rescheduled procedure.
Overdose
Due to the controlled clinical environment in which Nanocis is administered, overdose is highly unlikely. However, if an excessive amount of radioactivity were to be administered, the absorbed radiation dose to the patient could be reduced by encouraging frequent urination and adequate hydration to promote excretion and minimise radiation exposure. There is no specific antidote. The nuclear medicine physician would monitor the patient and provide supportive care as needed, including assessment of the radiation dose received.
Nanocis is always prepared and administered in a controlled clinical environment by trained nuclear medicine professionals. Patients should discuss any concerns about the procedure, including radiation exposure, with their nuclear medicine physician before the examination.
What Are the Side Effects of Nanocis?
Nanocis has a very favourable safety profile, and adverse reactions are uncommon. The following side effects have been reported based on post-marketing surveillance and clinical experience. As with all radiopharmaceuticals, the potential for allergic reactions exists, and appropriate emergency medications and equipment must be immediately available during administration.
Side effects are classified according to the MedDRA frequency convention used by the European Medicines Agency (EMA):
Very Rare
Affects fewer than 1 in 10,000 patients
- Urticaria (hives)
- Erythema (skin redness)
- Angioedema (swelling of face, lips, tongue, or throat)
- Pruritus (itching)
- Anaphylactic or anaphylactoid reactions
Not Known
Frequency cannot be estimated from available data
- Injection site pain or discomfort
- Local injection site reactions
Radiation-Related Considerations
Beyond the pharmacological side effects listed above, exposure to ionising radiation from any radiopharmaceutical carries a theoretical risk. The effective radiation dose from diagnostic nuclear medicine procedures with Nanocis is generally low, and the diagnostic benefit is expected to outweigh the radiation risk when the procedure is clinically indicated.
The specific absorbed doses to individual organs depend on the route of administration, the activity administered, and the patient's body habitus. Detailed dosimetry tables are available in the product's Summary of Product Characteristics (SmPC) and should be reviewed by the nuclear medicine physician as part of the benefit-risk assessment.
For sentinel lymph node procedures (subcutaneous/intradermal injection), the effective dose is typically very low because the majority of the radioactivity remains localised at the injection site and in the draining lymph nodes, with minimal systemic distribution.
When to Seek Immediate Medical Attention
- Difficulty breathing or swallowing
- Swelling of the face, lips, tongue, or throat
- Severe skin rash or widespread hives
- Dizziness, lightheadedness, or feeling faint
- Rapid heartbeat or palpitations
These symptoms may indicate an anaphylactic reaction and require immediate emergency treatment. While such reactions are extremely rare with Nanocis, nuclear medicine departments are equipped to manage them promptly.
Reporting Side Effects
If you experience any side effects after receiving Nanocis, it is important to report them. You can report side effects to your nuclear medicine physician, your national pharmacovigilance authority (such as the MHRA in the United Kingdom, the EMA in Europe, or the FDA in the United States), or through the Yellow Card Scheme or equivalent reporting system in your country. Reporting helps improve the safety knowledge of all medicines.
How Should Nanocis Be Stored?
Patients do not store Nanocis themselves. The product is stored under the responsibility of the nuclear medicine specialist in appropriate premises that comply with national regulations on radioactive materials. Nevertheless, understanding the storage requirements provides insight into the product's stability and handling.
Before Reconstitution (Unreconstituted Kit)
- Store at temperatures not exceeding 25°C
- Do not freeze
- Store in the original packaging to protect from light
- The unreconstituted kit itself is not radioactive and does not require radiation shielding
- Do not use after the expiry date stated on the packaging
After Radiolabelling
- Store below 25°C
- Use within 6 hours of preparation
- Store in accordance with national regulations for radioactive materials, including appropriate shielding
- The radiolabelled product should not be used after the expiry time stated on the label by the radiopharmacist
- Any unused product or waste material should be disposed of in accordance with local requirements for radioactive waste
The 6-hour shelf life after preparation is determined primarily by the physical half-life of technetium-99m (6.02 hours) and the need to maintain adequate radiochemical purity. As technetium-99m decays, the activity decreases, and the proportion of impurities may increase, potentially affecting image quality.
What Does Nanocis Contain?
Nanocis is supplied as a two-vial kit. Understanding its composition is important for healthcare professionals preparing the product and for identifying any potential allergens.
Vial A (Dark Brown Colloidal Solution)
| Component | Role | Amount |
|---|---|---|
| Rhenium sulphide | Active substance (colloidal carrier) | 0.24 mg (0.15 mg elemental rhenium) |
| Gelatine | Stabiliser | As per formulation |
| Ascorbic acid | Antioxidant | As per formulation |
| Sodium hydroxide | pH adjustment | As per formulation |
| Concentrated hydrochloric acid | pH adjustment | As per formulation |
| Water for injections | Solvent | As per formulation |
Vial B (White Freeze-Dried Powder)
| Component | Role |
|---|---|
| Sodium pyrophosphate decahydrate | Complexing agent |
| Stannous chloride dihydrate | Reducing agent (enables Tc-99m labelling) |
| Sodium hydroxide | pH adjustment |
| Concentrated hydrochloric acid | pH adjustment |
After Radiolabelling
When the contents of both vials are combined and radiolabelled with sodium pertechnetate (99mTc), the final preparation is technetium (99mTc) colloidal rhenium sulphide in solution, ready for administration. The stannous chloride in Vial B serves as a reducing agent that converts pertechnetate (Tc-99m in the +7 oxidation state) to a lower oxidation state, enabling it to bind to the rhenium sulphide colloid particles.
The product is supplied in packs containing 5 vials A and 5 vials B. Each pair of vials is used for a single preparation session, from which multiple patient doses can be drawn, depending on the activity of sodium pertechnetate added and the doses required for individual patients.
Nanocis contains gelatine as a stabiliser. Patients with known allergies to gelatine should inform their nuclear medicine physician before the procedure, as this may represent a potential source of hypersensitivity reactions.
Frequently Asked Questions About Nanocis
Nanocis is not a cancer treatment — it is a diagnostic tool used in cancer staging. After radiolabelling with technetium-99m, it is injected near tumour sites to identify sentinel lymph nodes, which are the first nodes to which cancer cells are likely to spread. By examining these nodes, surgeons and oncologists can determine whether the cancer has metastasised, which directly influences treatment planning. Nanocis is most commonly used in breast cancer and melanoma staging, but is also used for vulvar, penile, prostate, and head and neck cancers.
The Nanocis kit itself (before preparation) is not radioactive. However, during preparation, it is mixed with sodium pertechnetate containing technetium-99m, a radioactive isotope that emits gamma radiation. After radiolabelling, the final product is radioactive. Technetium-99m has a short physical half-life of approximately 6 hours, meaning the radioactivity decreases rapidly and is essentially negligible within 24 to 48 hours after administration. The radiation dose from sentinel lymph node procedures is generally very low.
The injection itself takes only a few minutes. However, imaging with a gamma camera typically begins 15 minutes to 2 hours after injection, depending on the protocol and clinical indication. For sentinel lymph node procedures, some institutions use a one-day protocol (injection and surgery on the same day) while others use a two-day protocol (injection the day before surgery). The total time you spend in the nuclear medicine department for the injection and imaging portion is usually 1 to 3 hours.
You may feel some discomfort at the injection site, similar to any subcutaneous or intradermal injection. For breast cancer sentinel node procedures, the injection is given around the tumour or around the areola. Some patients report mild stinging or burning at the injection site, which typically resolves within a few minutes. For melanoma procedures, the injections are given intradermally around the tumour site, usually at multiple points. Your nuclear medicine physician can discuss pain management options if you are concerned.
Nanocis has one of the smallest and most uniform particle sizes (mean approximately 23–25 nm) among commonly used nanocolloid preparations. This compares favourably with Nanocoll (human serum albumin nanocolloid, particles <80 nm) and unfiltered technetium-99m sulfur colloid (particles 100–1000 nm, commonly used in North America). The smaller particle size of Nanocis contributes to efficient lymphatic drainage and faster sentinel node uptake. Each product has its own regulatory approvals and is preferred in different regions based on local practice and availability.
Yes. The amount of radioactivity used in sentinel lymph node procedures is very small, and the radiation exposure to people near you is negligible. Unlike therapeutic nuclear medicine procedures (such as radioiodine treatment for thyroid cancer), diagnostic procedures with Nanocis do not require isolation or special precautions around others, including pregnant women and children. Your nuclear medicine physician will provide specific guidance based on the activity administered.
References
- European Medicines Agency (EMA). Core Summary of Product Characteristics for Technetium (99mTc) Nanocolloid Preparations. Available at: www.ema.europa.eu
- CIS bio international (Curium Group). Nanocis 0.24 mg – Summary of Product Characteristics (SmPC). Available at: www.curiumpharma.com
- Health Products Regulatory Authority (HPRA). Patient Information Leaflet – NANOCIS 0.24 mg Kit for Radiopharmaceutical Preparation. Available at: www.hpra.ie
- Paganelli G, et al. Sentinel node detection in breast cancer: pre-operative and intra-operative use of 99mTc-labelled colloid particles. European Journal of Nuclear Medicine. 2003;30(5):633-638.
- Uren RF, et al. Lymphatic drainage of the skin and breast detected by lymphoscintigraphy using 99mTc-rhenium sulphide colloid. Clinical Nuclear Medicine. 2003;28(5):371-377.
- Tsopelas C, Sutton R. Why certain dyes are useful for localizing the sentinel lymph node. Journal of Nuclear Medicine. 2002;43(10):1377-1382.
- World Health Organization (WHO). Guidelines on Radiation Protection in Nuclear Medicine. Geneva: WHO; 2024.
- European Association of Nuclear Medicine (EANM). Paediatric Dosage Card. EANM; 2023. Available at: www.eanm.org
- Giammarile F, et al. The EANM and SNMMI Practice Guideline for Lymphoscintigraphy and Sentinel Node Localization in Breast Cancer. European Journal of Nuclear Medicine and Molecular Imaging. 2013;40(12):1932-1947.
- Mansel RE, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. Journal of the National Cancer Institute. 2006;98(9):599-609.
Editorial Team
This article was written by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in nuclear medicine, radiology, and oncology. All content has been reviewed according to international guidelines from the EMA, WHO, and EANM.
All content reviewed by board-certified physicians following the GRADE evidence framework. Evidence Level 1A based on systematic reviews and clinical guidelines.
Independent medical editorial content with no pharmaceutical company sponsorship. Following WHO, EMA, and EANM guidelines for nuclear medicine.