NanoHSA (Nanocolloidal Human Serum Albumin)

What Is NanoHSA and What Is It Used For?

NanoHSA is a radiopharmaceutical diagnostic agent containing nanosized particles of human serum albumin. When labeled with technetium-99m, it is used for sentinel lymph node detection (lymphoscintigraphy) in cancer surgery, most commonly for breast cancer and melanoma staging.

NanoHSA belongs to the class of radiopharmaceutical diagnostic agents. The product consists of a kit containing nanosized particles of human serum albumin (HSA), typically less than 100 nanometers in diameter. These particles are designed to be labeled with sodium pertechnetate containing the radioactive isotope technetium-99m (Tc-99m) in a nuclear medicine laboratory before use. Once prepared, the radiolabeled nanoparticles can be detected using specialized imaging equipment such as gamma cameras and intraoperative gamma probes.

The primary clinical application of NanoHSA is sentinel lymph node detection, also known as lymphoscintigraphy. In oncological surgery, the sentinel lymph node is defined as the first lymph node or group of nodes that receives lymphatic drainage from a primary tumor. Identifying and biopsying these sentinel nodes is a critical step in cancer staging because it helps determine whether cancer cells have spread beyond the primary tumor site. This information directly influences treatment decisions, including the extent of surgery needed and whether adjuvant therapies such as chemotherapy or radiation therapy are recommended.

NanoHSA is most commonly used in the following cancer types:

• Breast cancer: Sentinel lymph node biopsy has become the standard of care for clinically node-negative breast cancer, allowing patients to avoid unnecessary axillary lymph node dissection and its associated morbidity, including lymphedema
• Melanoma: Sentinel lymph node mapping is essential for staging cutaneous melanoma, helping identify patients who may benefit from further lymph node dissection or systemic therapy
• Head and neck cancers: Increasingly used for sentinel node detection in oral cavity cancers and other head and neck malignancies
• Gynecological cancers: Applications in cervical and endometrial cancer for pelvic sentinel lymph node mapping
• Penile and other urological cancers: Sentinel node detection for staging purposes

How does NanoHSA work?

After subcutaneous injection near the tumor site, the nanosized albumin particles enter the lymphatic capillaries due to their small size. The particles then migrate through the lymphatic channels and accumulate in the sentinel lymph nodes. Two primary mechanisms cause the particles to be retained in these nodes: phagocytosis (engulfment by macrophage immune cells within the node) and mechanical filtration through the node's reticular network.

The small particle size of NanoHSA (less than 100 nm) is a key advantage. Smaller colloid particles typically drain more rapidly through lymphatic channels compared to larger colloid preparations, allowing for faster identification of sentinel nodes. At the same time, they are still large enough to be retained effectively within the sentinel lymph node, providing a good balance between transit speed and node retention. This makes NanoHSA particularly suitable for same-day protocols where injection and surgery occur on the same day.

The technetium-99m label emits gamma radiation at an energy of 140 keV, which can be detected externally using a gamma camera for preoperative lymphoscintigraphic imaging or intraoperatively using a handheld gamma probe. The surgeon uses the gamma probe to locate the "hot" sentinel node during the operation, enabling precise identification and excision for pathological examination.

What Should You Know Before Receiving NanoHSA?

NanoHSA should only be administered by qualified nuclear medicine professionals. Key precautions include informing your doctor about any allergies to human albumin products, pregnancy or breastfeeding status, and any concurrent radiopharmaceutical procedures. The product involves exposure to ionizing radiation, which must be medically justified.

Before receiving NanoHSA, your medical team will evaluate whether the procedure is appropriate for your specific clinical situation. The decision to use any radiopharmaceutical involves balancing the diagnostic benefit against the small radiation risk. In the case of sentinel lymph node mapping for cancer staging, the clinical benefit of accurate staging far outweighs the minimal radiation exposure involved.

Contraindications

There are limited absolute contraindications to NanoHSA, but the following situations require careful consideration:

• Known hypersensitivity: Patients with a documented allergy to human serum albumin or any of the excipients in the preparation should not receive NanoHSA. Although allergic reactions are extremely rare, they are possible with any albumin-derived product
• Severe systemic infection at the injection site: Active infection in the area around the planned injection site may affect lymphatic drainage patterns and compromise the accuracy of sentinel node identification
• Pregnancy (relative contraindication): Radiopharmaceutical procedures are generally avoided during pregnancy unless the expected clinical benefit clearly outweighs the potential risk to the fetus from ionizing radiation

Warnings and Precautions

Several important precautions apply to the use of NanoHSA:

• Radiation safety: NanoHSA, when labeled with Tc-99m, involves exposure to ionizing radiation. All procedures must follow the ALARA principle (As Low As Reasonably Achievable), meaning the minimum dose necessary for a diagnostic result should be used. Staff handling the product must follow institutional radiation safety protocols
• Blood-derived product: Since NanoHSA contains human serum albumin derived from human blood, standard precautions for blood-derived products apply. Manufacturing processes include steps to reduce the risk of transmitting infectious agents, but a theoretical risk cannot be entirely eliminated
• Allergic reactions: Although rare, hypersensitivity reactions including anaphylaxis are theoretically possible. Facilities performing the procedure should have emergency resuscitation equipment and trained personnel available
• Imaging interpretation: The nuclear medicine physician must be aware that certain factors can affect lymphatic drainage patterns, including prior surgery in the region, radiation therapy, or inflammatory conditions. These factors should be communicated before the procedure
• Quality control: The radiolabeled preparation must undergo quality control testing (radiochemical purity assessment) before administration to ensure adequate labeling efficiency

Pregnancy and Breastfeeding

The use of NanoHSA labeled with Tc-99m during pregnancy requires careful risk-benefit assessment. Ionizing radiation can potentially harm the developing fetus, and therefore radiopharmaceutical procedures should be avoided during pregnancy unless absolutely necessary for the mother's care. If sentinel lymph node mapping is considered essential (for example, in a pregnant patient with newly diagnosed breast cancer), the procedure may be performed after thorough discussion between the patient, her obstetrician, the oncologist, and the nuclear medicine physician. Studies have shown that the radiation dose to the fetus from sentinel node procedures is very low, typically well below thresholds associated with adverse fetal effects.

For breastfeeding mothers, temporary interruption of breastfeeding is recommended after receiving Tc-99m-labeled NanoHSA. The duration of interruption depends on the administered activity and should be determined by the nuclear medicine physician, but typically ranges from 4 to 24 hours. Expressed breast milk during this period should be discarded. The healthcare team will provide specific guidance based on the individual circumstances.

How Does NanoHSA Interact with Other Drugs?

NanoHSA has very few known drug interactions. The main concern is concurrent use of other radiopharmaceuticals, which may interfere with imaging results. Certain medications and prior treatments such as surgery or radiation to the injection area can affect lymphatic drainage and the accuracy of sentinel node detection.

Because NanoHSA is a diagnostic agent rather than a therapeutic drug, it has a fundamentally different interaction profile compared to most medications. The product is not metabolized by hepatic enzymes, does not bind to drug receptors, and does not circulate systemically at pharmacologically active concentrations. Nevertheless, several factors can influence the quality and accuracy of sentinel lymph node mapping when using NanoHSA.

Factors Affecting Procedure Accuracy

Medications That May Affect Results

While there are no direct pharmacological drug interactions with NanoHSA, certain medications can indirectly influence sentinel lymph node mapping outcomes. Immunosuppressive therapies may affect the phagocytic function of macrophages within lymph nodes, potentially altering tracer retention. Patients receiving high-dose corticosteroids or other immunosuppressive agents should inform their nuclear medicine team. Additionally, certain chemotherapeutic agents given as neoadjuvant therapy before surgery may affect lymphatic drainage patterns, which is relevant when sentinel node biopsy is performed after neoadjuvant treatment.

It is always important to provide your medical team with a complete list of all medications, supplements, and treatments you are currently receiving or have recently received. This allows the nuclear medicine physician and surgeon to plan the procedure optimally and interpret results accurately.

What Is the Correct Dosage of NanoHSA?

NanoHSA dosage is determined by the nuclear medicine physician based on the type of cancer, injection site, and timing relative to surgery. Typical injected activities range from 10 to 150 MBq of Tc-99m-labeled NanoHSA, depending on whether a same-day or next-day surgical protocol is used. The product is never self-administered.

The dosage of NanoHSA is expressed in terms of radioactivity (measured in megabecquerels, MBq) rather than conventional drug doses (milligrams), because the pharmacological effect depends on the radioactive label rather than the mass of albumin nanoparticles. The nuclear medicine physician determines the appropriate dose for each patient based on several factors including the type of cancer, the injection site, the expected time interval between injection and surgery, and institutional protocols.

Standard Dosing Protocols

Adults

In adult patients, the standard approach for breast cancer involves a peritumoral or periareolar injection of Tc-99m-labeled NanoHSA. The injected activity typically ranges from 10 to 40 MBq for same-day protocols or 40 to 150 MBq for day-before protocols (the higher activity compensates for radioactive decay overnight). The product is injected in a small volume (typically 0.2 to 0.5 mL) at one to four sites around the tumor or areola. For melanoma, injections are placed intradermally around the primary tumor site or biopsy scar.

Following injection, a dynamic and static lymphoscintigraphic imaging session is performed using a gamma camera. The images allow the nuclear medicine physician to identify the sentinel lymph node(s) and their anatomical location, which is then marked on the patient's skin to guide the surgeon. Intraoperatively, the surgeon uses a handheld gamma probe to confirm the location of the radioactive sentinel node and excise it for pathological analysis.

Children

Sentinel lymph node mapping with radiopharmaceuticals is less commonly performed in pediatric patients, as the cancers typically requiring this procedure (breast cancer, melanoma) are primarily adult diseases. When sentinel node procedures are indicated in children or adolescents (for example, in pediatric melanoma), the injected activity is reduced proportionally based on body weight or body surface area, following established pediatric nuclear medicine dosing guidelines such as those published by the European Association of Nuclear Medicine (EANM) Dosage Card. The decision to proceed with the procedure in a pediatric patient requires careful consideration by a multidisciplinary team including pediatric oncologists and nuclear medicine specialists.

Elderly

No specific dose adjustment is required for elderly patients. However, the nuclear medicine physician should consider that lymphatic drainage may be slower in older adults, potentially requiring longer intervals between injection and imaging or surgery. Co-morbidities common in elderly patients do not typically affect the radiopharmaceutical's distribution, but may influence the overall surgical plan and risk-benefit assessment for sentinel node biopsy.

Missed Dose

The concept of a "missed dose" does not apply to NanoHSA in the traditional pharmaceutical sense, as it is a single-administration diagnostic agent used in a controlled hospital environment. If the procedure is delayed or cancelled after the radiopharmaceutical has been prepared, the preparation may need to be discarded due to radioactive decay of Tc-99m (half-life approximately 6 hours), and a fresh preparation would be required for a rescheduled procedure. The nuclear medicine department coordinates timing carefully with the surgical team to ensure optimal conditions.

Overdose

Accidental overdose with NanoHSA is extremely unlikely given the controlled hospital setting in which it is administered. In the unlikely event that an excessive activity of Tc-99m-labeled NanoHSA is administered, the primary concern would be increased radiation exposure. The nuclear medicine physician would assess the estimated radiation dose to the patient and implement appropriate monitoring. Fortunately, the short half-life of Tc-99m (approximately 6 hours) means that excessive radioactivity decreases rapidly through natural physical decay. Encouraging adequate hydration and frequent voiding can help accelerate the clearance of any systemically absorbed radioactivity.

What Are the Side Effects of NanoHSA?

Side effects from NanoHSA are rare. The most commonly reported effects include mild pain or discomfort at the injection site. Allergic reactions are very rare but possible. The radiation exposure from Tc-99m labeling is minimal, with an effective dose typically less than 1 mSv.

NanoHSA is generally very well tolerated. Because it is a diagnostic agent administered as a small-volume subcutaneous injection, systemic side effects are uncommon. The albumin nanoparticles remain predominantly at the injection site and within the lymphatic system, with minimal systemic absorption. The following side effects have been reported in clinical use and post-marketing surveillance:

Radiation-related considerations

As with all radiopharmaceuticals, the administration of Tc-99m-labeled NanoHSA involves exposure to ionizing radiation. However, the radiation dose from sentinel lymph node procedures is very low. The effective dose to the patient is typically less than 1 millisievert (mSv), which is comparable to the natural background radiation received in a few months of normal life. For context, a standard chest X-ray delivers approximately 0.02 mSv, while a CT scan of the abdomen delivers approximately 8–10 mSv.

The injection site receives the highest localized radiation dose since most of the radioactive tracer remains at the injection point. The absorbed dose to the injection site is estimated at approximately 10–30 milligray (mGy) depending on the injected activity, which is considered clinically insignificant and does not cause radiation injury to the skin or subcutaneous tissue.

The radiation exposure to the sentinel lymph nodes themselves, as well as to nearby tissues, is very low. Importantly, handling the excised sentinel lymph node specimen in the pathology laboratory does not pose a significant radiation risk to laboratory personnel, provided standard nuclear medicine waste handling protocols are followed.

When to contact your medical team

Although serious adverse reactions to NanoHSA are extremely rare, you should contact your medical team if you experience any of the following after the injection:

• Signs of an allergic reaction such as widespread skin rash, hives, difficulty breathing, or swelling of the face, lips, or tongue
• Significant pain, redness, or swelling at the injection site that worsens or does not improve
• Fever or chills developing within hours of the injection
• Any other unexpected symptoms that concern you

How Should NanoHSA Be Stored?

NanoHSA kits must be stored according to the manufacturer's specifications, typically at controlled room temperature or refrigerated. Once labeled with Tc-99m, the preparation must be used within a defined time period (usually 6–8 hours). All storage and handling is performed by hospital pharmacy or nuclear medicine staff.

As a hospital-only product, storage of NanoHSA is managed entirely by the nuclear medicine department or hospital pharmacy. Patients do not need to store this product. However, the following storage requirements are important for healthcare professionals:

• Unlabeled kit: Store the NanoHSA kit at controlled room temperature (15–25°C / 59–77°F) or refrigerated (2–8°C / 36–46°F) according to the manufacturer's specific instructions. Protect from light. Do not freeze
• After Tc-99m labeling: The radiolabeled preparation should be used within 6–8 hours of preparation (or as specified by the manufacturer's summary of product characteristics). Store at room temperature in an appropriately shielded container
• Radiation shielding: All radioactive preparations must be stored in lead-lined containers or behind lead shielding to minimize radiation exposure to staff, in accordance with institutional radiation safety protocols
• Waste disposal: Unused radiolabeled product and any contaminated materials must be disposed of according to local regulations for radioactive waste. Due to the short half-life of Tc-99m, waste is typically stored for decay (approximately 10 half-lives, or about 60 hours) before disposal as standard clinical waste
• Expiry date: Do not use the NanoHSA kit after the expiry date printed on the packaging. Check the date before each preparation

The nuclear medicine department maintains strict quality control procedures for all radiopharmaceutical preparations. Before each patient administration, the radiolabeled NanoHSA undergoes quality control testing to verify adequate radiochemical purity (typically required to exceed 95%). If quality control criteria are not met, the preparation is discarded and a new one is prepared.

What Does NanoHSA Contain?

The NanoHSA kit contains nanosized particles of human serum albumin as the active ingredient, along with excipients necessary for the formulation. The kit is designed to be reconstituted with sodium pertechnetate (99mTc) to produce the radiolabeled diagnostic agent.

Active ingredient

The active pharmaceutical ingredient in NanoHSA is nanosized human serum albumin (HSA). Human serum albumin is the most abundant protein in human blood plasma, and when processed into nanoparticles (typically less than 100 nm in diameter), it forms the carrier for the technetium-99m radioactive label. The albumin is derived from human blood donations and undergoes rigorous manufacturing processes including pasteurization and viral inactivation steps to ensure safety.

Excipients

The NanoHSA kit typically contains the following excipients in addition to the active nanoparticle component:

• Stannous chloride dihydrate (SnCl₂·2H₂O): Acts as the reducing agent necessary for the radiolabeling process. Stannous (tin) ions reduce pertechnetate (TcO₄⁻) from its +7 oxidation state to lower oxidation states, enabling it to bind to the albumin nanoparticles
• Sodium chloride: Provides isotonicity to the reconstituted solution
• Buffer components: Maintain appropriate pH for optimal radiolabeling efficiency and product stability
• Nitrogen atmosphere: The kit vial is typically sealed under a nitrogen atmosphere to prevent oxidation of stannous ions, which would reduce labeling efficiency

The exact composition and quantities of excipients may vary depending on the manufacturer and specific product formulation. Healthcare professionals should refer to the manufacturer's summary of product characteristics (SmPC) for complete compositional details. Patients with known sensitivities to any of these components should inform their nuclear medicine physician before the procedure.

Physical characteristics of the nanoparticles

The defining characteristic of NanoHSA is the nanosized particle diameter of the albumin colloid. The particles are typically less than 100 nanometers in diameter, with most preparations targeting a median particle size in the range of 20–80 nm. This small particle size distinguishes NanoHSA from other colloid radiopharmaceuticals used for sentinel node detection, which may have larger particle sizes. The small size contributes to rapid lymphatic uptake and efficient transit to sentinel lymph nodes, while the protein nature of albumin ensures biocompatibility and biodegradability within the body.

Frequently Asked Questions About NanoHSA