What is Radioactive Iodine (I-131)?

What is Radioactive Iodine (I-131)?

Radioactive iodine (I-131) is a radioactive isotope of iodine that emits both beta and gamma radiation, used therapeutically to ablate thyroid tissue and treat thyroid cancer by delivering targeted radiation to thyroid cells that concentrate iodine. 1, 2

Mechanism of Action

• I-131 is selectively taken up by thyroid follicular cells, exploiting the thyroid's natural iodine concentration mechanism 2
• The isotope simultaneously emits two types of radiation: beta minus (β-) particles for therapeutic tissue destruction and gamma (γ) rays for diagnostic imaging 2
• Beta particle penetration is limited to approximately 2mm in tissue, restricting the damaging effects primarily to thyroid cells while sparing surrounding structures 2
• The therapeutic effect occurs through direct cellular damage from ionizing radiation, leading to cell death in targeted thyroid tissue 3, 2

Clinical Applications in Thyroid Cancer

I-131 is administered after thyroidectomy for three distinct purposes 1:

1. Remnant Ablation

• Destroys residual normal thyroid tissue remaining after surgery, facilitating subsequent surveillance 1
• Enables more accurate serum thyroglobulin monitoring by eliminating normal thyroid tissue that could produce thyroglobulin 4
• Increases sensitivity of follow-up whole-body scans for detecting recurrent or metastatic disease 4

2. Adjuvant Therapy

• Targets potential microscopic residual tumor cells not visible on imaging 1
• Decreases locoregional recurrence risk in appropriately selected patients 1
• The post-therapeutic whole-body scan obtained after I-131 administration provides highly sensitive disease detection 1

3. Treatment of Known Metastatic Disease

• Treats documented locoregional lymph node metastases and distant metastases when they retain iodine-avid properties 1
• Approximately 70% of radioiodine-avid locoregional lymph nodes and pulmonary micrometastases respond to treatment 1

Dosing

Standard ablation doses range from 1110-1850 MBq (30-50 mCi) to 3700 MBq (100 mCi) 1:

• Lower doses (1850 MBq/50 mCi) are equally effective as higher doses (3700 MBq/100 mCi) for remnant ablation, even in patients with lymph node metastases, while reducing whole-body radiation exposure 1
• The choice between low and high activity should consider the clinical context, though recent evidence supports lower activities for most ablation scenarios 1

Risk-Stratified Use

I-131 administration is recommended based on recurrence risk stratification 1:

• High-risk patients (gross extrathyroidal extension, incomplete resection, distant metastases): I-131 is clearly indicated 1, 5
• Intermediate-risk patients: Decision should be individualized based on specific tumor features 1
• Low-risk patients: Controversial, with ongoing debate between major societies 1
• Very low-risk patients (unifocal tumors <1 cm, favorable histology, no extrathyroidal extension or lymph node metastases): I-131 is not indicated 1

Preparation Requirements

Adequate thyroid-stimulating hormone (TSH) stimulation is essential for effective I-131 uptake 1:

• Recombinant human TSH (rhTSH) is the preferred preparation method, allowing patients to remain on levothyroxine therapy 1
• rhTSH preparation demonstrates equal efficacy to levothyroxine withdrawal while providing better patient quality of life 1
• rhTSH was approved by the European Medicine Agency in 2005 and FDA in 2007 for remnant ablation preparation 1

Adverse Effects and Complications

Acute Effects (occurring within days to weeks) 6, 4:

• Nausea and vomiting are common immediate side effects 6
• Salivary gland swelling and pain from radiation sialadenitis 6
• Ageusia (loss of taste) occurs acutely 6

Long-term Complications 6, 4:

• Recurrent sialadenitis with xerostomia (dry mouth) is the most common chronic complication 6
• Dental caries secondary to reduced salivary flow 6
• Nasolacrimal outflow obstruction affecting tear drainage 6
• Pulmonary fibrosis in patients with diffuse lung metastases receiving high cumulative doses 6
• Second primary malignancies with increased risk at higher cumulative doses 6, 4
• Gonadal effects including temporary oligospermia in men and potential ovarian dysfunction in women 4

Radiation Exposure Considerations 1, 2:

• High doses of I-131 (>20 mGy) are associated with increased risk of hypothyroidism in exposed populations 1
• Gamma radiation emission requires radiation safety precautions for both patients and healthcare personnel 2
• Treatment may be conducted on inpatient or outpatient basis depending on dose and local regulations 2

Common Pitfalls to Avoid

• Do not use I-131 in very low-risk patients where it provides no demonstrated benefit and exposes patients to unnecessary radiation 1
• Do not assume all thyroid cancer requires I-131 therapy—the decision must be based on validated risk stratification systems 1
• Do not overlook the importance of adequate TSH stimulation—insufficient TSH levels result in poor I-131 uptake and treatment failure 1
• Do not ignore cumulative dose effects—patients receiving multiple high-dose treatments face increased risks of long-term complications including second malignancies 6, 4