Scintimun (Besilesomab): Anti-Granulocyte Monoclonal Antibody for Bone Infection Imaging

What Is Scintimun and What Is It Used For?

Scintimun is a specialised diagnostic radiopharmaceutical developed for nuclear medicine imaging of infection and inflammation. Each pack contains a vial of lyophilised (freeze-dried) besilesomab, a mouse-derived monoclonal antibody, together with a vial of reducing agent. When the antibody is radiolabelled with technetium-99m (^99mTc), it becomes a targeted imaging agent that binds to a specific antigen on the surface of human white blood cells (granulocytes) and can pinpoint sites where these cells have accumulated due to infection or inflammation.

Scintimun is marketed by CIS bio international, part of the Curium Group, and received a centralised marketing authorisation from the European Medicines Agency (EMA) in 2010. It belongs to the pharmacotherapeutic class of diagnostic radiopharmaceuticals for infection and inflammation detection, identified by ATC code V09HA03. Unlike therapeutic radiopharmaceuticals designed to deliver cytotoxic radiation to diseased tissues, Scintimun is purely diagnostic: it produces images that help physicians make more accurate clinical decisions without itself treating any disease.

The clinical rationale for Scintimun is based on a fundamental feature of the immune response. When bacteria invade bone tissue, the body recruits granulocytes — particularly neutrophils — to the site of infection. These cells release enzymes and inflammatory mediators that create a characteristic focus of increased cellular activity. A radiolabelled anti-granulocyte antibody that can home to these cells provides a sensitive way to localise active infection, even when conventional anatomical imaging (such as X-ray or CT) is inconclusive or when the imaging findings overlap with those of non-infectious conditions such as fracture, tumour, or aseptic loosening of a prosthesis.

Approved Clinical Indication

The approved European indication for Scintimun is:

• Scintigraphic imaging, in conjunction with other appropriate imaging modalities, for the diagnosis and localisation of inflammation or infection in peripheral bone in adults with suspected osteomyelitis.

Several clarifications are important for correct clinical use:

• Scintimun is indicated for peripheral bone, which means the appendicular skeleton (arms and legs) rather than the axial skeleton (skull, vertebrae, ribs, sternum). Imaging of the axial skeleton with Scintimun is less reliable because physiological bone marrow uptake is substantial and can obscure pathological findings.
• Scintimun is not recommended for the diagnosis of diabetic foot infection. The reason is that the diagnostic performance of granulocyte imaging in this setting has not been adequately established, and dedicated protocols using labelled autologous leukocytes are generally preferred.
• Scintimun should always be used in conjunction with other appropriate imaging techniques such as plain radiography, computed tomography (CT), or magnetic resonance imaging (MRI). Functional imaging provides complementary information about cellular activity, while anatomical imaging reveals structural changes.

How Does Scintimun Work?

Besilesomab is a murine monoclonal IgG1 antibody produced by the BW 250/183 hybridoma cell line. It binds with high specificity to non-specific cross-reacting antigen 95 (NCA-95), a 95 kDa glycoprotein also known as CEACAM8 or CD66b, which belongs to the carcinoembryonic antigen (CEA) family. NCA-95 is expressed predominantly on the surface of mature human granulocytes and their precursors in the bone marrow. It is not expressed on lymphocytes, monocytes, or most other cell types, which gives besilesomab its specificity for this leukocyte lineage.

After intravenous injection of the radiolabelled antibody, a proportion of the dose binds in vivo to circulating granulocytes within the bloodstream. Studies indicate that roughly 10–20% of the administered radioactivity attaches to circulating cells, while a further fraction binds directly to granulocyte precursors in the bone marrow. The remainder circulates as free antibody until it is either bound, metabolised, or excreted. This mixed distribution pattern — partly cell-bound, partly free-circulating — distinguishes besilesomab imaging from techniques that use ex vivo labelled autologous leukocytes, where all of the radioactivity is initially cell-associated.

At sites of active infection or inflammation, local capillary permeability is increased, and granulocytes migrate out of the bloodstream into the affected tissue. As these cells accumulate at the infectious focus, the radiolabelled antibody travels with them, producing a localised increase in radioactivity that is visible as a "hot spot" on gamma camera images. Delayed imaging at 24 hours often enhances the contrast between pathological uptake and background activity as free antibody is cleared from the circulation.

Technetium-99m itself is a well-suited radionuclide for diagnostic imaging: it emits gamma photons at 140 keV (ideal for standard gamma cameras), has a physical half-life of approximately 6.02 hours (short enough to minimise radiation dose but long enough for delayed imaging), and decays to the much longer-lived but much less radioactive technetium-99. The combination of a highly specific targeting molecule (besilesomab) and an optimal imaging isotope (^99mTc) makes Scintimun a powerful tool in the diagnostic workup of suspected bone infection.

Where Scintimun Fits in the Diagnostic Pathway

Osteomyelitis is notoriously difficult to diagnose, particularly in chronic cases or after orthopaedic surgery. Plain radiographs may remain normal for up to two weeks after the onset of acute osteomyelitis and cannot reliably distinguish infection from other causes of bone destruction. MRI offers excellent anatomical detail but may not differentiate active infection from post-surgical change, oedema, or marrow fibrosis. CT is useful for identifying cortical erosion and sequestra but shares similar specificity limitations.

Functional imaging with a radiolabelled anti-granulocyte agent such as Scintimun provides a direct readout of active cellular inflammation at the site. This information is particularly valuable when a patient has persistent symptoms despite previous treatment, when prior surgery has altered normal anatomy, or when clinical and laboratory findings are equivocal. Scintimun is therefore usually reserved for problem-solving situations rather than first-line screening, and the final diagnostic interpretation relies on correlation between the scintigraphic findings and conventional imaging.

What Should You Know Before Receiving Scintimun?

Because Scintimun contains a foreign protein (a murine antibody) and involves exposure to ionising radiation, a careful safety assessment is required before administration. The nuclear medicine physician performs a benefit–risk analysis for each patient individually, weighing the diagnostic information that may be obtained against the risks of hypersensitivity, radiation exposure, and antibody induction.

Contraindications

Scintimun must not be used in the following situations:

• Hypersensitivity to besilesomab, to murine proteins, or to any of the excipients listed in the product composition. Patients with a history of severe allergic reactions to mouse-derived products, including other murine monoclonal antibodies, are at particular risk.
• Positive test for human anti-mouse antibodies (HAMA). HAMA are antibodies that a human immune system produces against murine proteins after previous exposure. A positive HAMA test indicates prior sensitisation and substantially increases the risk of severe hypersensitivity reactions on re-administration, as well as leading to immune-complex formation that can distort the scintigraphic images.
• Pregnancy, whether confirmed or suspected. The product contains radioactive material after reconstitution, and the gamma radiation from technetium-99m reaches the foetus, carrying theoretical teratogenic and oncogenic risks.

Warnings and Precautions

The following precautions must be observed in every patient who receives Scintimun:

• Hypersensitivity reactions. Any radiopharmaceutical, and especially those containing foreign proteins, can cause hypersensitivity or anaphylactic reactions. Resuscitation equipment, corticosteroids, antihistamines, epinephrine (adrenaline), and oxygen must be immediately available during and after the injection. Patients should be observed in the nuclear medicine department for an appropriate period after administration.
• HAMA formation. After a single injection of Scintimun, approximately 14% of patients develop detectable HAMA. These antibodies persist for months to years and may preclude future administration of Scintimun or other murine-derived products. Patients and referring physicians should be informed of this limitation.
• Pre-administration HAMA testing. A HAMA test should be performed before the first administration if the patient has previously received any murine antibody product, and routinely before any second or subsequent administration of Scintimun.
• Radiation safety. Only authorised personnel working in facilities that meet national regulations for the safe use of radioactive materials may prepare and administer Scintimun. All procedures must comply with the ALARA principle (As Low As Reasonably Achievable) to minimise radiation exposure to patients and staff.
• Hydration and voiding. Adequate fluid intake and frequent voiding in the hours following injection help to reduce the radiation dose to the bladder wall and promote elimination of any free technetium that is not bound to the antibody.
• Paediatric use. The safety and efficacy of Scintimun in children and adolescents under 18 years of age have not been established in adequate clinical trials. Off-label use in this population requires particular caution and strong clinical justification.
• Concomitant haematological conditions. Conditions that alter granulocyte numbers or function (such as severe neutropenia, granulocyte colony-stimulating factor therapy, or active haematological malignancy) may affect the distribution of the tracer and should be taken into account when interpreting images.

Pregnancy and Breastfeeding

Pregnancy. Scintimun is strictly contraindicated during pregnancy. When a nuclear medicine procedure is proposed for a woman of childbearing potential, pregnancy must be actively excluded. The usual practice is to ask about the date of the last menstrual period and, when there is any doubt, to perform a pregnancy test before administration. If a procedure is nevertheless considered indispensable in a pregnant patient, an alternative imaging strategy that does not involve radiation (such as MRI) should almost always be preferred.

Breastfeeding. If administration of Scintimun to a breastfeeding mother is deemed clinically necessary, breastfeeding should be interrupted and the expressed milk discarded. The resumption of breastfeeding should be discussed with the nuclear medicine physician; based on the physical half-life of technetium-99m (approximately 6 hours), interruption for at least 12 hours is generally recommended, though local protocols may specify longer intervals depending on the administered activity. Direct contact with the infant should also be limited during this period to reduce external radiation exposure.

Fertility. No specific fertility studies with besilesomab have been performed. As with all procedures involving ionising radiation, the dose to the gonads should be kept as low as reasonably achievable.

Ability to Drive and Use Machines

Scintimun has no known direct effects on the ability to drive or operate machinery. However, patients who experience post-injection symptoms such as dizziness or anxiety should not drive immediately after the procedure. Because the examination is conducted in a hospital and includes imaging sessions that may extend over several hours or a return visit the next day, most patients plan their transport accordingly.

How Does Scintimun Interact with Other Drugs?

Formal drug–drug interaction studies with besilesomab have not been performed. Because the antibody acts by binding to a surface antigen on granulocytes rather than through a conventional pharmacological pathway, it is not expected to interact with commonly used medicines at the metabolic or pharmacokinetic level. Nevertheless, the clinical accuracy of the examination depends on the normal availability and behaviour of granulocytes, and several categories of drugs can influence this system. Patients should therefore provide a complete medication history — including prescription drugs, over-the-counter medicines, and herbal or dietary supplements — to the nuclear medicine team before the examination.

Medications That May Affect Scintimun Imaging

Important Considerations Before the Examination

Because Scintimun images are often used to guide decisions about antibiotic therapy or surgery, accurate interpretation depends on a full understanding of the patient's clinical context. The referring physician and the nuclear medicine specialist usually coordinate closely to determine the optimal timing of the scan relative to antibiotic courses, chemotherapy cycles, and any other immune-modulating treatments.

Patients should also tell the nuclear medicine team about any previous exposure to mouse-derived products, including therapeutic monoclonal antibodies of murine or chimeric origin, earlier Scintimun administrations, or experimental agents used in clinical trials. Such exposures increase the probability of pre-existing HAMA and therefore inform the decision about whether additional testing is needed before the scan.

There are no known interactions between Scintimun and commonly used non-immunomodulatory medications such as antihypertensives, oral hypoglycaemics, lipid-lowering drugs, or analgesics. Patients can generally continue their regular medications unless specifically instructed otherwise by the nuclear medicine physician.

What Is the Correct Dosage of Scintimun?

Scintimun is not self-administered. The preparation (reconstitution and radiolabelling of besilesomab with sodium pertechnetate), quality control, and administration are performed exclusively by authorised nuclear medicine specialists in facilities designed for the safe handling of radioactive materials. The dose is expressed primarily in megabecquerels (MBq) of technetium-99m, not in milligrams of besilesomab, because the diagnostic effect depends on the radioactivity rather than on the mass of antibody.

The typical preparation sequence involves reconstituting the lyophilised besilesomab vial with the provided reducing agent solution, adding freshly eluted sodium pertechnetate (^99mTc), gently mixing, and allowing the labelling reaction to complete at room temperature. Quality control (determination of radiochemical purity by thin-layer chromatography) is mandatory, and the radiolabelled product must meet the specified purity threshold (generally ≥95%) before it can be administered to patients. The radiolabelled product should be used within 3 hours of preparation and must be stored below 25°C during this time.

Adults

The activity can be reduced in smaller adults, frail patients, or those with lower expected disease activity, in line with the ALARA principle. The nuclear medicine physician balances image quality against radiation exposure when selecting the administered activity for each individual patient.

Children and Adolescents

The safety and efficacy of Scintimun in children and adolescents below 18 years of age have not been established. There are no robust clinical data to support a dosing recommendation in this age group, and the product information does not provide paediatric dosage guidance. Use in children is therefore generally off-label and requires specific clinical justification, a careful benefit–risk discussion with parents or guardians, and dose calculations based on the European Association of Nuclear Medicine (EANM) paediatric dosage card where an alternative radiopharmaceutical cannot be substituted.

Elderly Patients

No specific dose adjustment is required on the basis of age alone in adult patients. Standard adult doses apply to elderly patients. However, the nuclear medicine physician evaluates each individual's overall health, renal function, and the balance between diagnostic benefit and radiation exposure before administration. Elderly patients may also be more likely to have received previous murine antibody products, underlining the importance of HAMA testing.

Renal and Hepatic Impairment

Besilesomab is a protein molecule that is cleared primarily by uptake of bound antibody with granulocytes into the reticuloendothelial system and by catabolism of free antibody. It is not significantly cleared by the kidneys or metabolised by hepatic cytochrome P450 enzymes. Formal studies in patients with renal or hepatic impairment have not been conducted, but severe impairment is unlikely to necessitate a change in the administered activity. As always, the overall clinical picture should guide individualisation of dose.

Missed Dose

The concept of a missed dose does not apply to Scintimun in the conventional sense, because the product is given as a single diagnostic administration in a clinical setting. If a scheduled appointment is cancelled, the radiolabelled product cannot be stored for later use: after 3 hours it should no longer be administered, and after a longer interval the activity of technetium-99m decays significantly. A new preparation is required for a rescheduled examination.

Overdose

Overdose of Scintimun is highly unlikely because administration is controlled by trained nuclear medicine specialists in a hospital environment. In the event that an excessive amount of radioactivity is administered, the absorbed radiation dose to the patient can be reduced by encouraging frequent fluid intake and voiding to promote renal elimination of free ^99mTc. There is no specific antidote. The nuclear medicine physician monitors the patient, provides supportive care, and performs a dosimetric estimation of the additional radiation exposure. Dialysis is not expected to be useful in removing the antibody or cell-bound radionuclide.

What Are the Side Effects of Scintimun?

Scintimun has been studied in clinical trials involving several hundred patients and has a generally favourable safety profile. Nevertheless, because the active substance is a foreign (murine) protein, some adverse reactions are characteristic of this class and warrant specific attention. The frequency of adverse events is categorised according to the MedDRA convention used by the European Medicines Agency:

• Very common: ≥1 in 10 patients
• Common: ≥1 in 100 to <1 in 10 patients
• Uncommon: ≥1 in 1,000 to <1 in 100 patients
• Rare: ≥1 in 10,000 to <1 in 1,000 patients
• Very rare: <1 in 10,000 patients
• Not known: frequency cannot be estimated from available data

Human Anti-Mouse Antibody (HAMA) Formation

The development of HAMA is the most distinctive adverse event associated with Scintimun. Because besilesomab is a murine IgG1 antibody, a proportion of immunocompetent patients recognise it as a foreign protein and mount an adaptive immune response. This produces HAMA of various specificities, including anti-idiotype, anti-isotype, and anti-allotype antibodies. Roughly 14% of patients develop detectable HAMA within a few weeks of a single injection, and these antibodies may persist for many months.

HAMA do not usually cause symptoms by themselves, but their clinical significance is twofold. First, on re-exposure to Scintimun or another murine-derived product, they can trigger rapid immune-complex formation leading to hypersensitivity or anaphylactoid reactions. Second, even without overt reactions, HAMA bind to subsequently administered besilesomab in the circulation, altering its biodistribution and potentially reducing the diagnostic accuracy of repeat scans. For these reasons, HAMA testing is routinely recommended before any second administration of Scintimun, and a positive result is a contraindication to further exposure.

Radiation-Related Considerations

Beyond the pharmacological side effects, every diagnostic nuclear medicine procedure involves exposure to ionising radiation. For Scintimun at typical administered activities (400–800 MBq of ^99mTc), the effective dose to an average adult is in the range of several millisieverts, comparable to other established nuclear medicine examinations. The critical organ (the organ receiving the highest absorbed dose) is the spleen, followed by the bone marrow and the bladder wall. Detailed dosimetry is provided in the product's Summary of Product Characteristics and should be reviewed by the nuclear medicine physician during the benefit–risk assessment.

The theoretical lifetime cancer risk from a single diagnostic nuclear medicine examination is very small compared with the clinical benefit of an accurate diagnosis in patients with suspected osteomyelitis. Nonetheless, repeated studies using ionising radiation should be justified and optimised in every patient, and radiation-free modalities such as MRI should be considered where they can provide equivalent clinical information.

When to Seek Immediate Medical Attention

Reporting Side Effects

If you experience any side effects after receiving Scintimun, it is important to report them. You can report side effects to your nuclear medicine physician, to your national pharmacovigilance authority (such as the European Medicines Agency's EudraVigilance system, the UK Medicines and Healthcare products Regulatory Agency Yellow Card Scheme, the US Food and Drug Administration MedWatch programme, or the equivalent scheme in your country), or through the hospital's internal safety system. Reporting helps improve the safety knowledge of all medicines for future patients.

How Should Scintimun Be Stored?

Patients do not store Scintimun themselves. The product is stored under the responsibility of the hospital pharmacy or nuclear medicine department in premises that meet national regulatory requirements for radioactive materials and biological products. The storage requirements nevertheless provide useful insight into the product's stability and handling.

Before Reconstitution (Unreconstituted Kit)

• Store in a refrigerator at 2–8°C
• Do not freeze
• Keep the vials in the outer carton to protect from light
• The unreconstituted kit itself is not radioactive and does not require radiation shielding
• Do not use after the expiry date printed on the packaging

After Radiolabelling

• Store the reconstituted, radiolabelled product below 25°C
• Use within 3 hours of preparation
• Store in accordance with national regulations for radioactive materials, including appropriate lead shielding
• Do not use the radiolabelled product after the expiry time stated on the vial label by the radiopharmacist
• Dispose of any unused radiolabelled product and contaminated material as radioactive waste according to local regulations

The short shelf life of 3 hours after preparation is primarily determined by the physical half-life of technetium-99m (6.02 hours) and the need to maintain adequate radiochemical purity. As ^99mTc decays, the radioactivity decreases rapidly and the proportion of radioactive impurities may increase, both of which can compromise image quality.

Pharmaceutical waste management regulations require that any residual radioactive solution, syringes, gloves, and other contaminated materials be retained in shielded containers until the radioactivity has decayed to below background levels (generally after 24–48 hours) before final disposal through approved clinical waste routes.

What Does Scintimun Contain?

Scintimun is supplied as a two-vial kit for radiopharmaceutical preparation. Understanding the composition is important for healthcare professionals preparing the product and for identifying any potential sources of hypersensitivity in patients.

Vial 1 — Besilesomab (Lyophilised Powder)

Vial 2 — Labelling Reagent (Lyophilised Powder)

After Radiolabelling

When the contents of both vials are combined with freshly eluted sodium pertechnetate (^99mTc) and the labelling reaction is allowed to proceed at room temperature, the final product is technetium (^99mTc) besilesomab, a sterile solution ready for intravenous injection. The stannous chloride in Vial 2 serves as a reducing agent that converts pertechnetate (^99mTc in the +7 oxidation state) to lower oxidation states, allowing the radionuclide to bind to the antibody molecule via its disulfide bonds and associated groups. Radiochemical purity is verified by thin-layer chromatography before the product is released for patient use.

The pack provides sufficient material to prepare a single patient dose per kit, although the prepared product can be fractionated within its 3-hour shelf life if multiple patients are to be examined in sequence. Because each kit contains 1 mg of besilesomab and the typical administered protein mass is well below this amount, a single kit may yield more than one individual dose depending on local protocols.

Editorial Team

This article was written by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in nuclear medicine, radiology, infectious diseases, and orthopaedics. All content has been reviewed according to international guidelines from the EMA, WHO, and EANM and follows the GRADE framework for evidence assessment.