#1 Clinical Trials Search in Europe

FERUMOXTRAN-10

Ferumoxtran-10 (also known as Combidex or Ferrotran) is an innovative contrast agent being studied in clinical trials for cancer imaging. This ultra-small superparamagnetic iron oxide (USPIO) particle covered with a sugar coating is designed to enhance magnetic resonance imaging (MRI) scans. Ferumoxtran-10 has unique properties that allow it to travel through the bloodstream and accumulate in lymph nodes and other tissues, potentially improving the detection of cancer that has spread beyond its original site. Clinical trials are evaluating this agent’s effectiveness in detecting metastases in various cancers including brain tumors, prostate cancer, breast cancer, cervical cancer, and rectal cancer. This article explores how ferumoxtran-10 is being used in clinical research and its potential benefits for cancer diagnosis.

Table of Contents

What is Ferumoxtran-10?

Ferumoxtran-10 is a specialized contrast agent used in medical imaging, particularly in Magnetic Resonance Imaging (MRI). It’s also known by several other names including Combidex, Ferrotran, Sinerem, AMI-227, G-53425, and USPIO (Ultra-small Superparamagnetic Iron Oxide particles)[1][2].

This contrast agent consists of ultra-small iron oxide particles covered with a sugar coating (dextran). The particles are extremely tiny, which allows them to travel through blood vessels and into tissues that regular contrast agents might not reach[1].

How Ferumoxtran-10 Works

Ferumoxtran-10 works differently from conventional contrast agents. After being injected intravenously, these tiny particles circulate in the bloodstream and are eventually taken up by certain cells in the body, particularly those found in the liver, spleen, bone marrow, and lymph nodes[3].

What makes ferumoxtran-10 special is how it interacts with lymph nodes. In normal, healthy lymph nodes, specialized cells called macrophages absorb these particles. When viewed on an MRI scan 24-36 hours after injection, these healthy nodes appear dark due to the presence of iron[3][4].

However, if a lymph node contains cancer cells, those areas don’t absorb the particles, creating a contrast between the cancerous tissue (which remains bright) and the healthy tissue (which appears dark). This difference allows radiologists to identify potential cancer spread, even in normal-sized lymph nodes that might look unremarkable on conventional imaging[1].

Medical Applications

Ferumoxtran-10 is being studied for use in several types of cancer to detect the spread of disease to lymph nodes:

Brain Tumors

In patients with brain tumors, ferumoxtran-10 can help identify tumor boundaries and assess whether cancer has spread to nearby areas. It may provide better visualization of brain tumors and inflammatory lesions on MRI scans compared to standard contrast agents like gadolinium[1].

Because of its small size and ability to cross blood vessels into brain tumors, ferumoxtran-10 could potentially assist in future drug delivery treatments for brain tumors[1].

Prostate Cancer

In prostate cancer patients, ferumoxtran-10-enhanced MRI is being studied to detect pelvic lymph node metastases (cancer spread). This is particularly important for patients with intermediate to high risk of lymph node metastases who are scheduled for radical prostatectomy (surgical removal of the prostate) with extended pelvic lymph node dissection[2].

The goal is to improve detection of cancer spread before surgery, which could change treatment planning for these patients[2][4].

Genitourinary Cancers

Studies are evaluating the use of ferumoxtran-10 MRI (sometimes called MR lymphangiography) to detect metastases in lymph nodes for patients with bladder cancer and other genitourinary cancers[3].

Breast Cancer

Research is investigating how well ferumoxtran-10-enhanced MRI can identify metastases to the axillary (armpit) lymph nodes in patients with invasive breast cancer. It may also help evaluate changes in breast tumors after administration of the drug[4][5].

Rectal Cancer

Ferumoxtran-10 is being evaluated in combination with high-field strength MRI (7 Tesla) to detect lymph node metastases in rectal cancer with improved resolution[5].

Cervical and Endometrial Cancer

Studies are comparing ferumoxtran-10 MRI with other imaging techniques like PET/CT to detect lymph node metastases in patients with cervical and endometrial cancers[6].

Administration and Procedure

Ferumoxtran-10 is administered through an intravenous (IV) infusion. The typical dose is 2.6 mg of iron per kilogram of body weight, diluted in saline solution and infused slowly over 30 minutes[2][3].

The imaging procedure usually follows this timeline:

  1. Baseline MRI scan before receiving ferumoxtran-10
  2. Administration of ferumoxtran-10 through IV infusion
  3. Monitoring for 30 minutes to 2 hours after infusion for any reactions
  4. Follow-up MRI scan 24-36 hours later when the contrast agent has reached peak uptake in lymph nodes[3][4]

In clinical studies, the results of ferumoxtran-10 MRI are often compared with surgical pathology findings to determine the accuracy of the imaging technique[2][5].

Effectiveness

Current imaging techniques for detecting lymph node metastases rely mainly on size criteria (enlarged nodes are considered suspicious), but this approach has limitations. Small metastases in normal-sized nodes may be missed, and enlarged reactive nodes without cancer may be misidentified as metastatic[3].

Ferumoxtran-10-enhanced MRI aims to overcome these limitations by looking at the function of lymph nodes rather than just their size. Research studies are measuring the sensitivity (ability to correctly identify nodes with cancer) and specificity (ability to correctly identify nodes without cancer) of this technique compared to conventional imaging methods[6].

Some studies suggest that ferumoxtran-10 MRI may be particularly valuable for detecting small lymph node metastases (less than 5mm), though the diagnostic accuracy for these tiny metastases may still be lower than for larger ones[5].

Researchers are also exploring whether using higher-strength MRI machines (such as 7 Tesla instead of the standard 1.5 or 3 Tesla) in combination with ferumoxtran-10 could further improve detection of small metastases[5].

Safety Profile

As with any medical contrast agent, ferumoxtran-10 can cause side effects. Patients are typically monitored after receiving the infusion to watch for potential reactions[3].

Clinical trials are collecting data on the adverse effects of ferumoxtran-10. The safety profile appears to be a significant focus of the ongoing research, as this agent is still being evaluated by regulatory authorities like the FDA and has not yet received full approval for general clinical use[3].

Current Research Status

Ferumoxtran-10 is currently being investigated in multiple clinical trials. It’s important to note that this contrast agent is still considered investigational in many countries and has not yet received full regulatory approval for routine clinical use[3].

The research studies aim to validate the effectiveness of ferumoxtran-10-enhanced MRI compared to standard imaging techniques and surgical pathology findings. If successful, this imaging method could provide a non-invasive alternative to current lymph node staging techniques that often require surgery[5].

Additionally, the technique could potentially complement image-guided focal therapies targeting lymph node metastases, such as radiotherapy, and help improve treatment planning for cancer patients[5].

Aspect Details
Drug Name Ferumoxtran-10 (also known as Combidex, Ferrotran, Sinerem)
Classification Ultra-small superparamagnetic iron oxide (USPIO) contrast agent
Mechanism Iron oxide particles accumulate in normal lymph tissue but not in areas where cancer cells have replaced normal tissue, creating a contrast visible on MRI
Administration Intravenous infusion (typically 2.6 mg/kg) over 30-45 minutes
Imaging Timing MRI performed 24-36 hours after infusion for optimal contrast
Cancer Types Studied Brain tumors, prostate cancer, breast cancer, cervical cancer, endometrial cancer, rectal cancer
Primary Applications Detection of lymph node metastases, brain tumor imaging, improving cancer staging accuracy
Advantages Over Conventional Imaging Potential to detect metastases in normal-sized lymph nodes, better visualization of tumor boundaries, improved accuracy compared to size-based detection methods
Research Focus Diagnostic accuracy (sensitivity and specificity), comparison with standard imaging techniques, potential to change patient management plans
Current Status Investigational – being evaluated in clinical trials

FAQ

  • What is ferumoxtran-10 and how does it work? Ferumoxtran-10 is an ultra-small superparamagnetic iron oxide (USPIO) particle covered with a sugar coating. When injected intravenously, it circulates in the bloodstream and is taken up primarily by the liver, spleen, bone marrow, and lymph nodes. In healthy lymph nodes, specialized cells called macrophages absorb these particles, which changes how these nodes appear on MRI scans. If cancer cells have replaced the normal tissue in lymph nodes, the particles aren't absorbed in those areas, creating a contrast that helps radiologists identify potential metastases that might not be visible with conventional imaging techniques.
  • What types of cancer are being studied with ferumoxtran-10? Clinical trials are investigating ferumoxtran-10 for enhancing MRI detection of metastases in several cancer types, including brain tumors, prostate cancer, breast cancer, cervical cancer, rectal cancer, and endometrial cancer. The focus is primarily on detecting cancer spread to lymph nodes or, in the case of brain tumors, visualizing the tumors themselves and the surrounding tissue.
  • How is ferumoxtran-10 administered in clinical trials? In most clinical trials, ferumoxtran-10 is administered as an intravenous infusion at a dose of approximately 2.6 mg/kg of body weight, typically diluted in saline solution. The infusion is given slowly over 30-45 minutes. Patients then undergo MRI scanning 24-36 hours after the infusion, which allows time for the particles to accumulate in lymph nodes and other tissues. This timing is crucial for optimal imaging results.
  • What are the potential benefits of using ferumoxtran-10 compared to conventional imaging? Conventional imaging techniques like standard MRI or CT scans primarily rely on the size of lymph nodes to detect cancer spread, which has limitations in accuracy. Ferumoxtran-10-enhanced MRI can potentially detect cancer metastases in normal-sized lymph nodes that would otherwise be missed. This could lead to more accurate cancer staging, better treatment planning, and potentially improved patient outcomes. In brain tumors, it may help better visualize the boundaries between tumor and normal tissue, which is critical for surgical planning.
  • Are there any side effects or risks associated with ferumoxtran-10? As with many contrast agents, ferumoxtran-10 can cause side effects. Patients in clinical trials are typically monitored for several hours after infusion. Some trials report monitoring patients for adverse reactions, though specific side effects aren't detailed in the trial summaries. Common reactions to contrast agents may include mild allergic reactions, temporary changes in blood pressure, or localized reactions at the injection site. Clinical trials are partly designed to further evaluate the safety profile of this agent.

Ongoing Clinical Trials on FERUMOXTRAN-10

  • Study on the Safety and Dosage of Ferumoxtran-10 for Examining Lymph Nodes in Rectal Cancer Patients Using NanoEcho Imaging Device

    Recruiting

    1 1
    Investigated diseases:
    Investigated drugs:
    Sweden

  • Study of Ferumoxtran-10 Enhanced MRI for Detecting Lymph Node Metastases in Patients with Esophageal Cancer

    Not yet recruiting

    1 1
    Investigated drugs:
    The Netherlands

Glossary

  • Ferumoxtran-10: An ultra-small superparamagnetic iron oxide (USPIO) particle covered with a sugar coating, used as an MRI contrast agent. Also known by brand names Combidex, Ferrotran, or Sinerem.
  • USPIO: Ultra-small superparamagnetic iron oxide particles, a type of contrast agent that affects magnetic fields and changes the appearance of tissues on MRI scans.
  • Metastasis: The spread of cancer cells from the primary (original) site to other parts of the body, commonly to lymph nodes or other organs.
  • Lymph Node: Small, bean-shaped structures that are part of the immune system, filtering lymph fluid and containing white blood cells. They are common sites for cancer to spread to.
  • MRI (Magnetic Resonance Imaging): A medical imaging technique that uses a magnetic field and radio waves to create detailed images of organs and tissues within the body.
  • Contrast Agent: A substance used to improve the visibility of internal structures in imaging techniques like MRI or CT scans.
  • Lymphangiography: An imaging technique that uses contrast material to visualize lymphatic vessels and lymph nodes.
  • Tesla: A unit of measurement for magnetic field strength. Clinical MRI machines typically operate at 1.5 or 3 Tesla, while research settings may use 7 Tesla machines for higher resolution imaging.
  • PET Scan: Positron Emission Tomography, an imaging test that uses a radioactive drug (tracer) to show how tissues and organs are functioning.
  • Histopathology: The examination of tissue under a microscope to study the manifestations of disease, considered the gold standard for cancer diagnosis.
  • Sensitivity: In medical testing, the ability of a test to correctly identify those with the disease (true positive rate).
  • Specificity: In medical testing, the ability of a test to correctly identify those without the disease (true negative rate).
  • Radical Prostatectomy: Surgical removal of the entire prostate gland and some surrounding tissue, performed to treat prostate cancer.
  • Extended Pelvic Lymph Node Dissection (ePLND): A surgical procedure to remove lymph nodes in the pelvic region to check for cancer spread, particularly in prostate cancer patients.
  • Glioma: A type of tumor that starts in the glial cells of the brain or spine.

References

  1. https://clinicaltrials.gov/study/NCT00659334
  2. https://clinicaltrials.gov/study/NCT04261777
  3. https://clinicaltrials.gov/study/NCT00147238
  4. https://clinicaltrials.gov/study/NCT00107484
  5. https://clinicaltrials.gov/study/NCT02751606
  6. https://clinicaltrials.gov/study/NCT00416455