Na[¹³¹I]l

Radiopharmaceutical: Na[¹³¹I]I, Sodium[¹³¹I]iodide, sodium iodide (¹³¹I)

Nuclide: Iodine-131

Activity: 3.7-11.1 MBq/mL of thyroid tissue   or fixed activities 370-740 MBq

Administration: Oral or intravenous (i.v.)

5.2.1 Mechanism of uptake / drug biology

Uptake and organification of iodine for the production of thyroid hormone takes place in the thyroid. The protein responsible for iodide transport, the sodium/iodide symporter, is located at the basolateral plasma membrane of thyrocytes. Iodine is incorporated into thyroid hormones which are bound to thyroglobulin. In this form, it is stored in thyroid follicles. Certain other (glandular) tissues can also incorporate iodine, but organification is not possible in these tissues. There is no prolonged retention of iodine outside the thyroid. This distinction is used in therapeutic applications of Iodine-131

5.2.2 Patient selection

Patients with primary hyperthyroidism due to: Graves’ disease, solitary autonomous nodule (toxic adenoma), or toxic multinodular goitre.

Patients with nontoxic multinodular goitre with slight compression signs or symptoms not candidate for surgery or recurrent multinodular goitre after surgery.

The detailed recommendations are available in the EANM guidelines for therapy of benign thyroid disease [43].

5.2.3 Exclusion criteria

Contraindications

• Pregnancy. This is an absolute contraindication and must be excluded before Iodine-131 therapy is given. Therefore, female patients with reproductive capacity must have a pregnancy test on the day of therapy. This test can only be omitted in sterilized patients or patient older than 50 years.
• Lactation: Iodine-131 excretion in breast milk is substantial and would form an unacceptable Iodine-131 intake for an infant. Breastfeeding should be omitted for at least 3 weeks. Breast milk can be pumped and discarded during these 3 weeks.

Relative contraindications:

• Active and severe Graves’ ophthalmopathy.
• Uncontrolled hyperthyroidism
• Coexisting (or suspicion of) thyroid cancer.
• Reduced self-care.
• Childhood (age between 5-10 years). Some clinicians who manage childhood Graves’ disease are wary of using Iodine-131 therapy. There are, however, data from a study with nearly 40 years of follow-up that showed no increased risk of thyroid cancer or leukaemia in children and adolescents treated with Iodine-131.
• Low iodine uptake. When the 24-hour Iodine-131 uptake (RAIU) is significantly lower than expected (<20%, especially in patients with Graves’ disease), the following possibilities should be considered, and, in these cases, treatment with Iodine-131 might not be indicated:
  • medication has not been discontinued;
  • the patient is not hyperthyroid at present or the thyrotoxicosis is not primary hyperthyroidism.

5.2.4 Procedure

The requirement to admit patients due to administered Iodine-131 activity varies considerably across different countries.

Patients with symptoms of Graves’ ophthalmopathy must be referred to an ophthalmologist before Iodine-131 treatment.

Numerous drugs, foods and cosmetics may affect the iodine uptake. In some cases, these must be discontinued for a certain period of time. If the patient has had a recent CT-scan with iodine-containing contrast, Iodine-131 must be postponed for at least 4-6 weeks.

Anti-thyroid drug therapy with thiamazol in patients with hyperthyroidism (whether or not in combination with thyroxine) should be, if clinically feasible, discontinued 3-5 days prior to Iodine-131 treatment and may be resumed 3 days after Iodine-131 therapy. Anti-thyroid therapy with Propylthiouracil (PTU) must be discontinued for at least 15 days because of its negative effect on Iodine-131 treatment.

If necessary, beta-blockers can be prescribed in symptomatic hyperthyroid patients. This medication does not have to be interrupted during Iodine-131 therapy. Thiamazol and thyroxine must also be discontinued for 3-5 days and PTU for at least 15 days prior to Iodine-131 uptake measurement(s) (and for scintigraphy).

During the first 24 h, the patient is advised to drink extra and thereby thus minimize the radiation dose to the bladder.

The therapeutic effect of the Iodine-131 treatment (with respect to the reduction of thyroid function) usually occurs within 3-6 months. Thyroid function should be monitored within that period so thyrostatic treatment can be adjusted in a timely fashion. If the first treatment has insufficient effect, subsequent Iodine-131 treatment is recommended.

5.2.5 Dosimetry

Within the range of administered activities of Iodine-131, low absorbed doses to normal tissues are delivered [91]. Thus, normal tissue dosimetry is not usually required.

In some cases, fixed activities are delivered, whereas in other cases administered activities are calculated with different methods:

• Measurement of thyroidal volume and/or Iodine-131 uptake measurement after 24 h;
• Measurement of thyroidal volume, Iodine-131 uptake, and individual Iodine-131 half-life by at least two uptake measurements, for example, after 24 h and 5 days.

To determine the absorbed dose to the target, the Quimby-Marinelli method has been widely used [92]. Moreover, the EANM Dosimetry Committee has released standard operational procedures for dosimetry prior to Iodine-131 therapy [38].

Treatments aimed to deliver an absorbed dose prescribed to the target have shown high success rates [93].

• Graves’ disease
  • The success rate has proved to be dependent on the absorbed dose prescribed to the target [94,95]. Moreover, function-orientated Iodine-131 treatments have aimed to deliver an absorbed dose to achieve euthyroidism. A common approach is to deliver an ablative absorbed dose to the thyroid [96].
• Autonomous adenoma
  • Delivery of absorbed doses of 300 Gy and 400 Gy to the solitary hyperfunctioning nodule has shown similar high success rates (> 90%) in the elimination of its functional autonomy [97].
• Multinodular goitre
  • In toxic multinodular goitre, intended absorbed doses above 150 Gy have resulted in success rates higher than 90% [98,99]. Cure rates could be maintained with absorbed doses around 120 Gy (28). In the case of nontoxic multinodular goitre a notable volume reduction was observed (>50%) [100].

Determination of the activity to administer in order to deliver a prescribed absorbed dose to the target is feasible and has been widely reported [43]. The target mass can be determined by ultrasound. Following the administration of a tracer of Iodine-131, thyroid uptake with time has to be assessed [38]. If the uptake is determined with a thyroid probe, 2 MBq are sufficient, and up to 10 MBq may be needed if a gamma camera is used. These values may vary depending on national legislations and the volume may have to be determined with ^99mTc-pertechnetate scintigraphy. In any case, higher activities are not recommended due to the so-called ‘stunning’ effect [38]. The potential for semi-individualized treatment planning has been investigated using a mean half-life and patient specific uptake values [96]. A model to calculate the optimal absorbed dose to deliver based on the normal tissue complication probability (NTCP) was developed and verified [101].

Conventionally, 2D dosimetry has been the standard procedure. However, SPECT/CT acquisitions are widely available nowadays, which enables 3D dosimetry. Moreover, guidelines for SPECT dosimetry with Iodine-131 following the MIRD formalism are available [35].

5.2.6 Effectiveness

Treatments aimed to deliver an absorbed dose prescribed to the target have shown high success rates [93].

In Graves’ disease, the success rate has proved to be dependent on the absorbed dose prescribed to the target [94,95]. Moreover, function-orientated Iodine-131 treatments have aimed to deliver an absorbed dose to achieve euthyroidism. A common approach is to deliver an ablative absorbed dose to the thyroid [102].

In Autonomous adenoma, delivery of absorbed doses of 300 Gy and 400 Gy to the solitary hyperfunctioning nodule has shown similar high success rates (> 90%) in the elimination of its functional autonomy [97].

In toxic multinodular goitre, intended absorbed doses above 150 Gy have resulted in success rates higher than 90% [98,99]. Cure rates could be maintained with absorbed doses around 120 Gy (15). In the case of nontoxic multinodular goitre a notable volume reduction was observed (>50%) [100].

5.2.7 Side Effects

When using relatively low therapeutic doses, clinically relevant radiation thyroiditis and / or temporary worsening of thyrotoxicosis (mostly between 3 and 10 days) as a result of thyroid hormone emissions, are seen only incidentally. Thyroiditis (usually within a few weeks) can occur after Iodine-131 treatment of a large goitre, which can lead to swelling and trachea compression, sore throat, and stomatitis. The symptoms usually disappear within one week, the use of antiphlogistics could reduce symptoms.

If compression symptoms exist prior to Iodine-131 therapy and in case of mild endocrine opthalmopathia, prophylactic treatment with prednisolone is recommended for the prevention of critical obstructive complications and deterioration of EO. In higher doses, sialoadenitis (within 1 week) might form a possible complication which can usually be prevented by adequate stimulation of the salivary glands (e.g. use of sour sweets) during the first 2 days after Iodine-131 therapy. Gastritis might also occur (1-2 days after therapy), this can be treated with medication. Very rarely, transient laryngeal nerve dysfunction occurs.

In patients with (non)toxic multinodular goitre, Graves’ disease is occasionally induced by Iodine 131- treatment. This is a relatively rare complication of Iodine-131 therapy, which is probably caused by the emission of degraded thyroid cells, which start to function as antigen.

5.2.8 Status

Sodium[¹³¹I]iodide is approved in the EU for the treatment of Graves’ disease, solitary autonomous nodule (toxic adenoma), and toxic multinodular goitre.