Indium (In-111) Oxinate Curiumpharma
Radiopharmaceutical for diagnostic white blood cell and platelet labeling in nuclear medicine
Quick Facts About Indium (In-111) Oxinate
Key Takeaways
- Indium (In-111) oxinate is a radiopharmaceutical diagnostic agent used to label white blood cells and platelets for nuclear medicine imaging.
- It is used exclusively in licensed nuclear medicine facilities by trained professionals and is never directly injected into patients without prior cell labeling.
- The primary clinical applications include detecting hidden infections, abscesses, inflammatory bowel disease, and evaluating fever of unknown origin.
- Indium-111 emits gamma rays at 171 keV and 245 keV, with a physical half-life of 2.83 days, allowing imaging over 24-48 hours for high diagnostic accuracy.
- Radiation exposure is relatively low and the diagnostic benefits typically outweigh the risks; however, it should be avoided during pregnancy unless absolutely necessary.
What Is Indium (In-111) Oxinate and What Is It Used For?
Indium (In-111) oxinate Curiumpharma is a sterile, pyrogen-free radiopharmaceutical solution designed for the ex vivo labeling of autologous leukocytes (white blood cells) and thrombocytes (platelets). It belongs to the class of diagnostic radiopharmaceuticals and plays a critical role in nuclear medicine imaging for the detection and localization of inflammatory and infectious processes throughout the body.
The active component is a lipophilic complex of the radionuclide indium-111 with 8-hydroxyquinoline (oxine). This lipophilic property allows the complex to passively diffuse across cell membranes. Once inside the cell, indium-111 dissociates from the oxine carrier and binds to intracellular proteins and other cytoplasmic components, effectively trapping the radionuclide within the cell. The oxine is then released back into the extracellular space, where it can be removed during washing steps.
The labeled cells, once reinjected into the patient's bloodstream, behave like normal leukocytes or platelets. White blood cells naturally migrate to sites of infection and inflammation through chemotaxis, while platelets accumulate at sites of active thrombosis. Indium-111 emits gamma radiation at two distinct energy peaks — 171 keV (90% abundance) and 245 keV (94% abundance) — which can be detected by a gamma camera to produce diagnostic images showing where the labeled cells have concentrated.
Primary Clinical Indications
The clinical applications of In-111 labeled leukocyte scintigraphy are well established and supported by decades of clinical evidence. The primary indications include:
- Occult infection and abscess detection: In-111 leukocyte imaging is considered the gold standard for detecting intra-abdominal abscesses, soft tissue infections, and post-surgical infections that may not be apparent on conventional imaging.
- Fever of unknown origin (FUO): When standard diagnostic workup fails to identify the source of persistent fever, In-111 labeled white blood cell scanning can help localize occult infectious or inflammatory foci.
- Inflammatory bowel disease (IBD): The technique is used to assess disease activity and extent in Crohn's disease and ulcerative colitis without the need for invasive endoscopy.
- Osteomyelitis: Particularly useful for detecting bone infections, especially in the peripheral skeleton and in patients with prosthetic joint infections.
- Vascular graft infection: Evaluation of suspected infections of synthetic vascular grafts and endovascular prostheses.
- Endocarditis: As an adjunct to echocardiography in diagnosing infective endocarditis, particularly in patients with prosthetic heart valves.
In-111 Labeled Platelet Imaging
Beyond leukocyte labeling, indium-111 oxinate is also used for platelet (thrombocyte) labeling. In-111 labeled platelet studies provide valuable information about platelet kinetics, lifespan, and sites of platelet destruction or consumption. Clinical applications of platelet labeling include evaluation of deep vein thrombosis, assessment of platelet survival in thrombocytopenic disorders, detection of active thrombus formation in cardiac chambers and on prosthetic heart valves, and monitoring of antiplatelet therapy effectiveness.
The procedure for platelet labeling requires meticulous technique to ensure adequate labeling efficiency while maintaining platelet viability and function. Platelet-rich plasma is separated from whole blood, incubated with In-111 oxinate, and then reinjected after appropriate washing to remove unbound activity.
What Should You Know Before Taking Indium (In-111) Oxinate?
Because Indium (In-111) oxinate Curiumpharma is used exclusively in controlled nuclear medicine settings by trained healthcare professionals, most safety considerations are managed by the clinical team. However, patients should be fully informed about the procedure, its benefits, risks, and any preparation requirements.
Contraindications
There are relatively few absolute contraindications to In-111 leukocyte or platelet imaging, but certain conditions require careful evaluation:
- Known hypersensitivity to any component of the preparation, including 8-hydroxyquinoline (oxine) or indium chloride.
- Severe leukopenia (very low white blood cell count) may make leukocyte labeling technically impractical and yield insufficient labeled cells for diagnostic imaging.
- Severe thrombocytopenia (very low platelet count) may preclude platelet labeling studies, and the blood draw itself could pose bleeding risks.
- Patients who cannot tolerate blood withdrawal due to severe anemia, hemodynamic instability, or other clinical factors.
Warnings and Precautions
Several important precautions apply to the use of Indium (In-111) oxinate:
- Aseptic technique: Strict aseptic technique must be maintained throughout the cell labeling process to prevent contamination of the blood product that will be reinjected into the patient. Any breach in sterility could result in bacteremia or sepsis.
- Cell viability: The labeling procedure must be carried out carefully to maintain cell viability and function. Excessive concentrations of In-111 oxinate or prolonged incubation times can damage cells and reduce labeling efficiency.
- Radiation dose consideration: As with all radiopharmaceutical procedures, the radiation dose to the patient should be kept as low as reasonably achievable (ALARA principle) while obtaining diagnostically adequate images.
- Antibiotic therapy: Current antibiotic treatment may reduce the sensitivity of the scan by suppressing the inflammatory response and reducing leukocyte migration to infection sites. The referring clinician and nuclear medicine physician should discuss whether antibiotics should be temporarily withheld.
- Corticosteroid therapy: Corticosteroids can suppress leukocyte function and migration, potentially leading to false-negative results.
- Recent blood transfusion: Recent transfusion may affect the results of platelet labeling studies.
Pregnancy and Breastfeeding
Radiopharmaceutical procedures involving ionizing radiation should generally be avoided during pregnancy unless the potential diagnostic benefit clearly outweighs the risk to the fetus. The European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) recommend that pregnancy should be excluded before any nuclear medicine procedure in women of childbearing potential.
If a scan with In-111 labeled cells is deemed absolutely necessary during pregnancy, the radiation dose to the fetus should be carefully estimated and documented. Alternative imaging modalities that do not involve ionizing radiation, such as ultrasound or magnetic resonance imaging (MRI), should be considered first.
For breastfeeding mothers, a temporary interruption of breastfeeding may be recommended following the procedure. The duration of interruption depends on the administered activity and should be determined by the nuclear medicine physician. Expressed breast milk during the interruption period should be discarded. According to international guidelines, a cessation of breastfeeding for at least 24 hours is commonly recommended, though some guidelines suggest longer periods depending on the specific activity administered.
How Does Indium (In-111) Oxinate Interact with Other Drugs?
Unlike conventional medications, Indium (In-111) oxinate does not undergo metabolic pathways that would lead to traditional pharmacokinetic drug interactions. However, various medications can significantly affect the diagnostic accuracy of In-111 labeled leukocyte and platelet imaging by altering cell function, migration patterns, or inflammatory responses.
| Medication Class | Effect on Scan | Clinical Significance | Recommendation |
|---|---|---|---|
| Antibiotics | Reduced leukocyte migration to infection sites | May cause false-negative results | Discuss with physician; may need temporary withholding |
| Corticosteroids | Suppressed leukocyte chemotaxis and function | Reduced sensitivity for infection detection | Cannot usually be stopped; note in report |
| Immunosuppressants (e.g., cyclosporine, tacrolimus) | Altered leukocyte count and function | May reduce labeling yield and scan accuracy | Document use; adjust interpretation accordingly |
| Anticoagulants (heparin, warfarin) | Affect platelet function and labeling | May affect platelet labeling studies specifically | Discuss timing with nuclear medicine physician |
| Antiplatelet agents (aspirin, clopidogrel) | Altered platelet activation and aggregation | May affect platelet labeling and kinetic studies | Note in clinical history; may affect interpretation |
| G-CSF / GM-CSF (growth factors) | Increased leukocyte count; altered migration patterns | May cause false-positive results in bone marrow | Note timing of administration relative to scan |
| NSAIDs | Mild suppression of inflammatory response | Generally minor effect | Usually does not require discontinuation |
It is essential that the nuclear medicine department is informed about all current medications before the procedure. The referring physician and nuclear medicine specialist should collaboratively decide whether any medications need to be temporarily adjusted. In most cases, the medications are documented and their potential effects are taken into account during image interpretation rather than requiring dose modification or discontinuation.
Interactions During the Labeling Process
Certain substances present in the blood sample can interfere with the in vitro labeling process itself. Heparin used as an anticoagulant during blood collection is a standard part of the procedure, but the type and concentration must be carefully controlled. Excessive heparin can impair cell labeling efficiency. Additionally, plasma proteins and transferrin can compete with intracellular binding, which is why careful washing of labeled cells is essential before reinjection.
What Is the Correct Dosage of Indium (In-111) Oxinate?
Dosing of Indium (In-111) oxinate is expressed in megabecquerels (MBq), the standard unit of radioactivity, rather than in milligrams as with conventional drugs. The administered activity is carefully calculated to balance diagnostic image quality with radiation dose to the patient, following the ALARA (As Low As Reasonably Achievable) principle.
Adults
Leukocyte (White Blood Cell) Imaging
The typical administered activity for In-111 labeled leukocyte scintigraphy in adults is 10-20 MBq (0.3-0.5 mCi). The activity used for labeling is typically higher (approximately 20-40 MBq added to the cell preparation) because not all activity binds to cells. After washing, the actual injected activity is usually in the 10-20 MBq range. Imaging is performed at 4 hours and 24 hours post-injection, with optional delayed imaging at 48 hours if needed for improved specificity.
Platelet Imaging
For In-111 labeled platelet studies, the administered activity is typically 3.7-18.5 MBq (0.1-0.5 mCi). Platelet labeling requires careful technique to maintain platelet viability. Imaging protocols vary based on the clinical question, with sequential images obtained over hours to days to assess platelet kinetics and survival.
Children
Pediatric Dosing
Pediatric doses are calculated based on body weight or body surface area, following the European Association of Nuclear Medicine (EANM) pediatric dosage card. The fraction of the adult dose is typically calculated as a percentage based on the child's weight. The minimum recommended activity should provide diagnostically adequate images. In-111 labeled leukocyte studies in children typically use 2-10 MBq depending on the child's weight, with a minimum of approximately 2 MBq to ensure diagnostic image quality.
Elderly
Geriatric Considerations
No specific dose adjustment is generally required for elderly patients. However, renal function assessment may be considered as impaired renal clearance can affect background activity levels. The standard adult activity range of 10-20 MBq applies. The nuclear medicine physician will take into account the patient's overall clinical status and any comorbidities that might affect image interpretation.
Missed Dose
The concept of a "missed dose" does not apply to In-111 oxinate in the traditional sense. Since this is a single-use diagnostic procedure administered in a controlled hospital setting, there is no repeat dosing schedule. If the labeled cells cannot be administered due to technical issues (e.g., labeling failure, contamination), the procedure may need to be rescheduled. A new blood sample would be required, and fresh In-111 oxinate would be used for the new labeling procedure.
Overdose
Inadvertent administration of excessive radioactivity is a recognized risk in nuclear medicine, although it is exceedingly rare with properly trained staff and quality assurance procedures. In the unlikely event of an overdose of In-111 labeled cells:
- Immediate assessment: Calculate the exact administered activity and estimate the radiation dose to critical organs (spleen, liver, red marrow).
- Hydration: Encourage increased fluid intake and frequent urination to promote excretion of any unbound indium-111.
- Monitoring: The patient should be monitored clinically, and the radiation dose should be documented.
- Reporting: The incident must be reported to the institutional radiation safety officer and relevant regulatory authorities.
- Follow-up: Long-term follow-up may be recommended depending on the magnitude of the excess dose.
What Are the Side Effects of Indium (In-111) Oxinate?
Indium (In-111) oxinate has a favorable safety profile when used according to established protocols. Since the product is used to label the patient's own (autologous) cells, the risk of immunological reactions is very low. Most reported adverse events are related to the blood collection and reinjection process rather than to the radiopharmaceutical itself.
Common
- Bruising or discomfort at the venipuncture site
- Mild pain during blood draw or reinjection
- Transient lightheadedness following blood withdrawal
Uncommon
- Mild fever following reinjection of labeled cells
- Localized hematoma at injection site
- Transient flushing
- Mild nausea
Rare
- Allergic-type reactions (e.g., urticaria, rash)
- Vasovagal episode during blood draw
- Transient hypotension
- Infection at the injection site (very rare with proper aseptic technique)
Radiation-Related Considerations
The radiation exposure from In-111 labeled cell studies, while kept to a minimum, carries a small theoretical risk of stochastic effects (effects where the probability, not severity, is proportional to dose). These include a very small increased lifetime risk of cancer. This risk must be weighed against the diagnostic benefit of the study. For a typical In-111 leukocyte scan delivering an effective dose of approximately 12 mSv, the additional lifetime cancer risk is estimated at approximately 0.06% (1 in 1,700), according to models published by the International Commission on Radiological Protection (ICRP).
It is important to note that deterministic effects (effects that occur above a threshold dose, such as skin erythema or organ damage) do not occur at the activity levels used in diagnostic In-111 procedures. The absorbed doses to individual organs are well below the thresholds for any deterministic radiation effects.
When to Contact Your Healthcare Provider
After an In-111 labeled cell procedure, patients should contact their healthcare provider if they experience:
- Signs of infection at the injection site (increasing redness, swelling, warmth, or purulent discharge)
- Persistent fever (above 38.5°C / 101.3°F) developing within 24-48 hours after the procedure
- Allergic symptoms such as widespread rash, facial swelling, or difficulty breathing
- Unusual or prolonged bleeding from the venipuncture site
How Should You Store Indium (In-111) Oxinate?
The storage of Indium (In-111) oxinate Curiumpharma is entirely the responsibility of the nuclear medicine department and radiopharmacy. Patients never receive this product for home use or self-administration. The storage requirements are governed by both pharmaceutical stability considerations and radiation safety regulations.
- Temperature: Store at controlled room temperature (15-25°C / 59-77°F) or according to the manufacturer's specific recommendations. Do not freeze.
- Radiation shielding: The product must be stored in appropriate lead or tungsten shielding containers to reduce radiation exposure to personnel.
- Security: Radioactive materials must be stored in secure, locked areas accessible only to authorized personnel, in compliance with national and institutional radiation safety regulations.
- Shelf life: The shelf life is determined by the radioactive decay of In-111 (physical half-life of 2.83 days). The product's usable activity decreases over time, and the expiry date on the label reflects the activity at a specified reference date and time.
- Labeling: Storage containers must be clearly labeled with the radionuclide identity, activity, reference date and time, and appropriate radiation warning symbols.
- Waste disposal: Expired or unused product must be disposed of in accordance with institutional radioactive waste management procedures and applicable national regulations.
What Does Indium (In-111) Oxinate Curiumpharma Contain?
Active Substance
The active substance is indium (In-111) oxinate, a lipophilic chelate complex formed by the coordination of indium-111 (a gamma-emitting radionuclide) with 8-hydroxyquinoline (oxine, also known as 8-quinolinol). The complex has the chemical formula In(C9H6NO)3. Indium-111 is an artificial radionuclide produced by cyclotron irradiation, typically through the nuclear reaction 112Cd(p,2n)111In or 111Cd(p,n)111In.
Physical Properties of Indium-111
| Property | Value |
|---|---|
| Physical half-life | 2.8047 days (67.31 hours) |
| Decay mode | Electron capture (100%) to Cadmium-111 |
| Gamma emission 1 | 171.3 keV (abundance 90.7%) |
| Gamma emission 2 | 245.4 keV (abundance 94.1%) |
| Daughter nuclide | Cadmium-111 (stable) |
| Production method | Cyclotron (proton bombardment of cadmium targets) |
Excipients and Solution Components
The complete formulation of Indium (In-111) oxinate Curiumpharma includes several components in addition to the active radiolabeled complex:
- 8-Hydroxyquinoline (oxine): The chelating agent that forms the lipophilic complex with indium-111, enabling cell membrane penetration.
- Hydrochloric acid and/or sodium hydroxide: Used for pH adjustment to maintain the solution within the appropriate pH range for cell labeling.
- Polysorbate 80 (Tween 80): A non-ionic surfactant that helps maintain the stability of the oxinate complex in solution.
- Water for injections: The solvent for the sterile preparation.
- HEPES buffer or acetate buffer: May be included to maintain pH stability during storage.
The solution is a clear, colorless to slightly yellow sterile preparation supplied in a glass vial with a rubber septum closure. The radionuclidic purity of indium-111 is typically greater than 99.9%, with trace amounts of indium-114m as the principal radionuclidic impurity. The radiochemical purity (proportion of activity in the form of In-111 oxinate complex) is specified to be above 95% at the time of manufacture.
Frequently Asked Questions
Indium (In-111) oxinate is a radiopharmaceutical used to label white blood cells (leukocytes) and platelets outside the body (ex vivo). Once labeled, these cells are reinjected into the patient and tracked using a gamma camera. This technique is primarily used to detect and localize hidden infections, abscesses, inflammatory bowel disease, osteomyelitis, vascular graft infections, and to evaluate fever of unknown origin. It is also used for platelet kinetic studies to assess platelet survival and sites of destruction.
The scan itself is not painful. The procedure involves two venipunctures (needle sticks): one to draw blood for labeling and one to reinfuse the labeled cells. These may cause brief discomfort similar to a routine blood test. The imaging sessions require lying still on the gamma camera bed for 30-60 minutes, which some patients may find uncomfortable but is not painful. No contrast agents or additional injections are typically required during the imaging portion.
The entire process spans approximately 24-48 hours. On the first day, blood is drawn and the white blood cells are separated and labeled (takes about 1-2 hours in the laboratory). The labeled cells are then reinjected. Initial imaging may be performed at 4 hours post-injection. The patient then returns the following day (at 24 hours) for a second imaging session. In some cases, a third imaging session at 48 hours may be required for improved diagnostic accuracy. Each imaging session takes approximately 30-60 minutes.
Yes, the radiation dose from In-111 labeled cell studies is relatively low, and you can generally resume normal activities and be around other people, including children and pregnant women, immediately after the procedure. The nuclear medicine department will provide specific radiation safety advice based on the activity administered. Unlike some other nuclear medicine procedures (such as radioiodine therapy), In-111 diagnostic studies do not typically require any isolation precautions or restrictions on close contact.
Both Indium-111 oxinate and Technetium-99m HMPAO (hexamethylpropyleneamine oxime) can be used to label white blood cells. In-111 has a longer half-life (2.83 days vs. 6 hours for Tc-99m), allowing delayed imaging at 24-48 hours, which significantly improves specificity for distinguishing infection from sterile inflammation. In-111 also provides better image quality for abdominal infections since it is not excreted through the bowel, unlike Tc-99m labeled cells which can show physiological bowel activity. However, Tc-99m offers higher photon flux for superior early imaging (1-4 hours), lower radiation dose per study, and is more widely available. The choice between the two depends on the clinical question and institutional expertise.
There are generally no specific dietary restrictions for In-111 labeled leukocyte or platelet studies. You can eat and drink normally before and after the procedure. However, you should inform the nuclear medicine department about any medications you are taking, as some may affect the scan results. Staying well hydrated after the procedure is recommended to help with overall comfort and to promote excretion of any free (unbound) indium-111 through the kidneys.
References
- European Association of Nuclear Medicine (EANM). Guidelines for Radiolabelling of Blood Components. EANM Procedure Guidelines. 2023. Available at: eanm.org
- Society of Nuclear Medicine and Molecular Imaging (SNMMI). Practice Guideline for the Use of In-111-Labeled White Blood Cells. Journal of Nuclear Medicine. 2022;63(12):1961-1969.
- International Commission on Radiological Protection (ICRP). Radiation Dose to Patients from Radiopharmaceuticals. ICRP Publication 128. Annals of the ICRP. 2015;44(2S).
- European Medicines Agency (EMA). Summary of Product Characteristics for Indium-111 Oxinate Radiopharmaceutical Preparations. Available at: ema.europa.eu
- World Health Organization (WHO). WHO Model List of Essential Medicines - Diagnostic Agents. 23rd List, 2023. Available at: who.int
- Roca M, de Vries EFJ,";"; F, Israel O, Signore A. Guidelines for the labelling of leucocytes with In-111-oxine. European Journal of Nuclear Medicine and Molecular Imaging. 2010;37(4):835-841. DOI: 10.1007/s00259-010-1393-5
- Ballinger JR. Short communication: are there clinically important drug interactions with radiopharmaceuticals? British Journal of Radiology. 2013;86(1023):20120665.
- Signore A, Jamar F, Israel O, et al. Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline. European Journal of Nuclear Medicine and Molecular Imaging. 2018;45(10):1816-1831.
- British Nuclear Medicine Society (BNMS). Clinical Guidelines for In-111 Labelled White Cell Imaging. Updated 2023. Available at: bnms.org.uk
- U.S. Food and Drug Administration (FDA). Indium In-111 Oxyquinoline Solution - Prescribing Information. Available at: accessdata.fda.gov
Editorial Team
This article has been written and reviewed by iMedic's medical editorial team, consisting of licensed specialist physicians with expertise in nuclear medicine, clinical pharmacology, and radiology.
iMedic Medical Editorial Team — Specialists in nuclear medicine and radiopharmaceuticals. All content follows the GRADE evidence framework and is based on international guidelines from EANM, SNMMI, ICRP, and WHO.
iMedic Medical Review Board — Independent panel of medical experts who review all content for accuracy, completeness, and adherence to current international guidelines and evidence-based medicine standards.
Conflict of Interest Statement: The iMedic editorial team has no financial relationships with pharmaceutical companies. All content is independently produced without commercial funding or advertising influence.