**7. 131I therapy of hyperthyroidism**

Hyperthyroidism is a consequence of an excess in free-thyroid hormone action on the tissues. The most frequent causes of hyperthyroidism are: Graves' Disease (GD), Toxic Adenoma (TA) or Toxic Multinodular Goiter (TMG). In any cases, hyperthyroidism can be caused by sub-acute thyroiditis or silent thyroiditis.

The treatment of GD, TA and TMG can be symptomatic with anti-thyroid drugs (often used as first line therapy) or definitive: radioiodine therapy (RaIT) or surgery (total or near-total thyroidectomy).

RaIT is a well established method for the treatment of hyperthyroidism; aim of the RaIT is to achieve an euthyroid or hypothyroid (such as in the Graves patients) status.

Presently, the optimal 131I activity to be administered is still matter of debate.

Many authors evaluated the effectiveness of different dosimetric methodologies. The results were variable and often controversial, in order to the frequency of recurrence and hypothyroidism (Regalbuto et al., 2009) (Giovannella, 2000).

In order to determine the 131I activity to be administered for the treatment of hyperthyroidism, fixed activity and adjusted activity approaches are currently employed. In

Internal Radiation Dosimetry: Models and Applications 37

Differentiated thyroid cancer (DTC) is the most common cancer of the endocrine system. The first line therapy is represented by total or near-total thyroidectomy (with dissect of the sixth lymph nodes level and, if necessary, of the lateral-cervical lymph nodes of the same

After Total or near-Total Thyroidectomy (nTT) it is useful to ablate the thyroid remnant with 131-radioiodine therapy (RaIT). In fact, several Authors, such as Mazzaferri et al. (1997) demonstrated that the *prognosis quod vitam* and the survival curve of the DTC-patients

In addition, the ablation of thyroid remnant (TRA) allows a better management of the

In fact, in the patients treated with TT or NTT and TRA, the Thyroglobulin (hTg) serum levels should be undetectable. Thus, any enhancement of hTg serum (both under L-T4 suppressive therapy or after exogenous TSH stimulation -rhTSH-) can be considered as a

However, the TRA activity can be adjusted through a dosimetric approach (Lassmann, 2010), which requires a pre-therapeutic scintigraphy with 131I or 124I PET. The dose to the

Both methods show advantages and disadvantages. The main disadvantage of the pretherapeutic scintigraphic method is correlated to the stunning or mass change effects that

On the other hand, the main disadvantage of the post-therapeutic scintigraphic method is correlated to technical difficulties such as the limitations deriving from the gamma-camera

The clinical evidence demonstrated that the dosimetry adjusted activities do not differ significantly from the fixed values. Thus, in the clinical practice, the dosimetric approach is not employed frequently. However, the dosimetric approach is useful for the treatment of

Dosimetry is particularly useful in patients with lung and/or bone metastases, where standard activities can lead to a radiation dose imparted to the lesions lower than the necessary. In such cases, it is necessary to acquire some whole scans starting from 6-7 hours

The development of bone metastases is commonly related to a serious reduction in quality of patient life because of pain occurrence and side effects of analgesics intake, especially

**9. Usefulness of radiopharmaceuticals for the palliation of painful bone** 

thyroid remnant can be calculated using 131I post-therapy whole body scan, too.

after radio-iodine therapy. (Eschmann et al., 2002) (Sgouros et al., 2004).

RaIT can be carried out in hypothyroidism state (TSH>=30) or after rhTSH stimulation. Post dose whole body scan and static images of the head, neck and thorax acquired 4-8 days after RIT allow to identify the thyroid remnant and metastases (loco-regional and/or distant). For the RaIT of TRA, fixed activities are employed more frequently: 1110, 2220 or 3700 MBq. In the patients treated after rhTSH stimulation it is necessary to employ a medium-to-high activity of radioiodine (2220 and 3700 MBq, respectively), because in this condition the effective half-life of radioiodine in the thyroid remnant is shorter than in the state of

**8. 131I therapy of differentiated thyroid carcinoma** 

significantly improve if RaIT follows TT or NTT.

could be determined by a diagnostic activity of 131I.

loco-regional and/or distant metastases.

side respect to primary lesion).

follow-up of these patients.

relapse of disease.

hypothyroidism.

dead time.

**metastases** 

both cases it is necessary, if possible, to suspend anti-thyroid drugs treatment 4-6 days before RaIT or thyroid scintigraphy.

The 131I "fixed"activity for RaIT is usually about 555 MBq. In such case, the thyroid scintigraphy with or without radioiodine thyroid uptake (RTU) curve can be not necessary.

In the adjusted activity approach, a dosimetric procedure is employed which requires two diagnostic steps: a) thyroid ultrasonography to calculate the volume of the gland, or the hot thyroid nodule(s), assuming for them an ellipsoidal shape; b) thyroid scintigraphy and RTU measurements after 131I tracer activity administration (1.8 MBq).

The dosimetric method most frequently employed was proposed by the MIRD commission (Snyder et al., 1975). In this approach, RTU measurements are usually conducted between 3 and 120 hours after administration. Multiple RTU measurements allow to calculate the effective half-life of the radioiodine into the hot nodules or in the whole gland (Figure 3).

In TMG and TA patients, the effective volume of the hot nodule(s) was calculated taking into account the presence of involving area(s) (whole nodule volume - involving area volume).

The radiation doses to be imparted to the gland (GD) or to the nodule(s) (TA and TMG) are up to 200 and 300 Gy, respectively.

In GD with ophtalmopathy, the radiation dose to be imparted must be adjusted, up to a maximum value of 250 Gy. In these patients, it is useful to administer anti-inflammatory drugs for a time duration ranging from 4 to 12 weeks after RaIT.

In all patients, the choice of the therapeutic dose will be determined also in function of: sex and age, type of hyperthyroidism (overt or sub-clinical) and its temporal duration, concomitant Hashimoto thyroiditis, anti-thyroid drugs therapy and its temporal duration. Basing on the above considerations, the activity to be administered can be calculated as:

$$A = 5.829 \frac{Dm}{\mathcal{U}\_{max} T\_{1/2 \text{eff}}} \tag{28}$$

where *A* is the activity to be administered in MBq in order to impart a dose *D* in cGy to the target (nodule or gland) of mass *m* in g, *Umax* is the maximum per cent radioiodine uptake (usually measured at 24 hours) and *T*1/2*eff* is the effective half-time in hours.

Recently, Amato et al. (2011) proposed an improved calculation method for the activity to be administered during the radioiodine treatment of hyperthyroidism. In this approach, a Monte Carlo simulation had been employed to derive the radiation dose in nodules or in the whole gland within an anthropomorphic phantom, taking into account the ellipsoidal shape of the target volumes.

As a result, the activity to be administered can be calculated with the formula:

$$A = \frac{Dm}{\mathcal{U}\_{\text{max}} T\_{1/2 \text{eff}}} \cdot \frac{32.31 \rho + 1}{\rho \left(0.2625 \rho + 5.1819\right)}\tag{29}$$

where we recall the definition of generalized radius, *ρ*=3*V*/*S*, stated in Equation 12, and here expressed in cm. The volume and the surface of the ellipsoidal target (nodule or thyroid lobe) can be calculated from the semiaxes measured through ultrasonography as:

4 3 *V = <sup>π</sup>abc* , () () () 1/ 4π 3 *<sup>p</sup> ppp ab + bc + ac S =* ⎛ ⎞ ⎜ ⎟ ⎝ ⎠ (30)

both cases it is necessary, if possible, to suspend anti-thyroid drugs treatment 4-6 days

The 131I "fixed"activity for RaIT is usually about 555 MBq. In such case, the thyroid scintigraphy with or without radioiodine thyroid uptake (RTU) curve can be not necessary. In the adjusted activity approach, a dosimetric procedure is employed which requires two diagnostic steps: a) thyroid ultrasonography to calculate the volume of the gland, or the hot thyroid nodule(s), assuming for them an ellipsoidal shape; b) thyroid scintigraphy and RTU

The dosimetric method most frequently employed was proposed by the MIRD commission (Snyder et al., 1975). In this approach, RTU measurements are usually conducted between 3 and 120 hours after administration. Multiple RTU measurements allow to calculate the effective half-life of the radioiodine into the hot nodules or in the whole gland (Figure 3). In TMG and TA patients, the effective volume of the hot nodule(s) was calculated taking into account the presence of involving area(s) (whole nodule volume - involving area

The radiation doses to be imparted to the gland (GD) or to the nodule(s) (TA and TMG) are

In GD with ophtalmopathy, the radiation dose to be imparted must be adjusted, up to a maximum value of 250 Gy. In these patients, it is useful to administer anti-inflammatory

In all patients, the choice of the therapeutic dose will be determined also in function of: sex and age, type of hyperthyroidism (overt or sub-clinical) and its temporal duration, concomitant Hashimoto thyroiditis, anti-thyroid drugs therapy and its temporal duration. Basing on the above considerations, the activity to be administered can be calculated as:

5.829

(usually measured at 24 hours) and *T*1/2*eff* is the effective half-time in hours.

As a result, the activity to be administered can be calculated with the formula:

*S =*

*A =*

4 3 *Dm A =*

where *A* is the activity to be administered in MBq in order to impart a dose *D* in cGy to the target (nodule or gland) of mass *m* in g, *Umax* is the maximum per cent radioiodine uptake

Recently, Amato et al. (2011) proposed an improved calculation method for the activity to be administered during the radioiodine treatment of hyperthyroidism. In this approach, a Monte Carlo simulation had been employed to derive the radiation dose in nodules or in the whole gland within an anthropomorphic phantom, taking into account the ellipsoidal shape

1/2

*U T* (28)

*max eff*

1/2 ( )

*max eff* 0.2625 5.1819 *Dm ρ+*

where we recall the definition of generalized radius, *ρ*=3*V*/*S*, stated in Equation 12, and here expressed in cm. The volume and the surface of the ellipsoidal target (nodule or thyroid lobe) can be calculated from the semiaxes measured through ultrasonography as:

> *V = <sup>π</sup>abc* , () () () 1/ 4π

32.31 1

3

⎛ ⎞ ⎜ ⎟ ⎝ ⎠

*<sup>p</sup> ppp ab + bc + ac*

*U T ρ ρ<sup>+</sup>* <sup>⋅</sup> (29)

(30)

measurements after 131I tracer activity administration (1.8 MBq).

drugs for a time duration ranging from 4 to 12 weeks after RaIT.

before RaIT or thyroid scintigraphy.

up to 200 and 300 Gy, respectively.

of the target volumes.

volume).
