Iodine-131 Metuximab in HCC Treatment |Open Medscience

Summary: ¹³¹I-Metuximab, marketed under the brand name Licartin, is a radiolabelled murine antibody developed for the treatment of hepatocellular carcinoma (HCC). Targeting the CD147 receptor, it delivers beta radiation directly to tumour cells, offering a novel therapeutic approach. Launched in China in 2006, Licartin remains available exclusively in that country. This article explores the development, mechanism of action, clinical efficacy, and future prospects of ¹³¹I-Metuximab in the management of HCC.

Introduction to Iodine-131 Metuximab

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of cancer-related deaths worldwide. Traditional treatment modalities, including surgery, chemotherapy, and radiotherapy, have limited efficacy due to late diagnosis and the tumour’s resistance to conventional therapies. The advent of targeted therapies has opened new avenues for HCC management. One such promising agent is ¹³¹I-Metuximab (Licartin), a radiolabelled antibody that combines immunotherapy with radiation therapy to target tumour cells selectively.

Hepatocellular Carcinoma: An Overview

HCC accounts for approximately 75–85% of primary liver cancers. Major risk factors include chronic hepatitis B and C infections, alcohol-induced liver cirrhosis, and non-alcoholic fatty liver disease. The asymptomatic nature of early-stage HCC often leads to late diagnoses, limiting treatment options and contributing to poor prognoses.

Challenges in Treatment

The complex vascular structure of the liver and the tendency of HCC to metastasise make surgical resection challenging. Systemic chemotherapy has limited effectiveness due to the liver’s detoxifying functions and the tumour’s inherent resistance mechanisms. Therefore, there is a critical need for therapies that can specifically target tumour cells without damaging healthy liver tissue.

CD147 as a Therapeutic Target

CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a transmembrane glycoprotein overexpressed in various tumour cells, including HCC. It plays a significant role in tumour progression, invasion, and metastasis by stimulating the production of matrix metalloproteinases (MMPs), which degrade the extracellular matrix.

Significance in HCC

The overexpression of CD147 in HCC makes it an attractive target for therapeutic intervention. By targeting CD147, it is possible to inhibit tumour growth and metastasis, offering a strategic advantage over non-specific therapies.

Development of ¹³¹I-Metuximab (Licartin)

Iodine-131 Metuximab is a murine monoclonal antibody that binds specifically to CD147. Developed in China, it combines the targeting capabilities of metuximab with the cytotoxic effects of radioactive iodine-131 (¹³¹I), a beta-emitting isotope.

Radiolabelling with Iodine-131

Iodine-131 is a well-established therapeutic radionuclide used in the treatment of thyroid disorders. Its beta radiation penetrates tissue over a short range, causing DNA damage and cell death in nearby tumour cells while minimising exposure to surrounding healthy tissue.

Launch and Availability

Licartin was launched in China in 2006 after demonstrating promising results in preclinical and clinical studies. As of now, it remains available exclusively in China.

Mechanism of Action

¹³¹I-Metuximab exerts its therapeutic effects through a two-pronged mechanism:

Targeted Binding to CD147: The metuximab antibody component binds specifically to CD147 receptors overexpressed on HCC cells. This specificity allows for the selective targeting of tumour cells.
Beta Radiation Emission: The iodine-131 component emits beta particles upon decay. These high-energy electrons cause direct DNA damage to the tumour cells, leading to apoptosis or necrosis.

Advantages of Combined Therapy

Enhanced Selectivity: The antibody ensures that radiation is delivered primarily to tumour cells, reducing collateral damage to healthy tissues.
Synergistic Effects: The combination of immunotherapy and radiotherapy may enhance overall efficacy compared to either modality alone.

Clinical Trials and Efficacy

Several clinical trials have evaluated the safety and efficacy of ¹³¹I-Metuximab in patients with HCC.

Phase I/II Trials

Early-phase trials focused on determining the optimal dosing, safety profile, and preliminary efficacy. These studies indicated that ¹³¹I-Metuximab is well-tolerated and shows anti-tumour activity in HCC patients.

Phase III Trials

In larger, randomised controlled trials, ¹³¹I-Metuximab demonstrated:

Improved Survival Rates: Patients receiving Licartin showed statistically significant increases in overall survival compared to control groups.
Reduced Recurrence: The treatment reduced the rate of tumour recurrence post-surgery or transarterial chemoembolisation (TACE).

Combination Therapies

Studies combining ¹³¹I-Metuximab with other treatments, such as TACE or surgical resection, have shown enhanced therapeutic outcomes, suggesting a potential role in multimodal treatment strategies.

Safety and Side Effects

¹³¹I-Metuximab has been generally well-tolerated in clinical studies. Common side effects include:

Hematological Toxicity: Temporary reductions in white blood cell and platelet counts due to bone marrow suppression.
Mild Radiation Sickness: Nausea, fatigue, and transient thyroid dysfunction related to radiation exposure.

Management of Adverse Effects

Monitoring Blood Counts: Regular monitoring allows for early detection and management of hematological toxicity.
Thyroid Protection: Administration of potassium iodide can protect the thyroid gland from radiation exposure.

Availability and Regulatory Status

As of the latest information, ¹³¹I-Metuximab is approved for use in China and is not yet available in other countries.

Reasons for Limited Availability

Regulatory Hurdles: Differences in regulatory requirements and the need for extensive clinical trials in other countries delay international approval.
Production Challenges: Radiolabelled antibodies require specialised facilities for production and handling due to their radioactive nature.

Future Prospects

The success of ¹³¹I-Metuximab in China paves the way for further research and potential global adoption.

Ongoing Research

International Clinical Trials: Efforts are underway to conduct multinational studies to evaluate efficacy and safety in diverse populations.
Combination Therapies: Research into combining ¹³¹I-Metuximab with newer targeted agents or immunotherapies is ongoing.

Potential for Other Cancers

Given CD147’s overexpression in various malignancies, there is potential to expand the use of ¹³¹I-Metuximab to other cancer types.

Conclusion

¹³¹I-Metuximab (Licartin) represents a significant advancement in the targeted treatment of hepatocellular carcinoma. By combining the specificity of antibody therapy with the cytotoxic effects of beta radiation, it offers a promising therapeutic option for patients with HCC. While currently available only in China, ongoing research and clinical trials may lead to its adoption in other countries, providing hope for improved outcomes in HCC management worldwide.

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