Evaluation of the dosimetry approaches in ablation treatment of thyroid cancer

Abstract In this study, we aimed to evaluate dosimetric approaches in ablation treatment of Differentiated Thyroid Carcinoma (DTC) without interrupting the clinical routine. Prior to therapy, 10.7 MBq 131I in average was orally given to 24 patients suffering from DTC. MIRD formalism was used for dosimetric calculations. For blood and bone marrow dosimetry, blood samples and whole‐body counts were collected at 2, 24, 72, and 120 h after I‐131 administration. For remnant tissue dosimetry, uptake measurements were performed at the same time intervals. To estimate the remnant volume, anterior and lateral planar gamma camera images were acquired with a reference source within the field of view at 24 h after I‐131 administration. Ultrasound imaging was also performed. Treatment activities determined with the fixed activity method were administered to the patients. Secondary cancer risk relative to applied therapy was evaluated for dosimetric approaches. The average dose to blood and bone marrow were determined as 0.15 ± 0.04 and 0.11 ± 0.04 Gy/GBq, respectively. The average remnant tissue dose was 0.58 ± 0.52 Gy/MBq and the corresponding required activity to ablate the remnant was approximately 1.3 GBq of 131I. A strong correlation between 24th‐hour uptake and time‐integrated activity coefficient values was obtained. Compared to fixed activity method, approximately five times higher secondary cancer risk was determined in bone marrow dosimetry, while the risk was about three times lower in lesion‐based dosimetry.

situation in most of nuclear medicine clinics. Suggested treatment activity for the ablation treatment varies from 0.9 to 7.4 GBq in the literature. [2][3][4][5][6] Recurrence ratios in the studies do not illustrate a significant difference in the patients who are applied 1.1-1.9 GBq RAI treatment and who are applied 1.9-7.4 GBq (7% and 9%, respectively). 1 One of the randomized prospective study shows that 81% of the patients have been ablated in their first treatment with 1.1 GBq RAI and this ratio is 84% with 3.7 GBq. 7 Hence, there is no certain treatment activity decided in the RAI treatment to ablate the remnant tissue based on the fixed activity method.
Nowadays, the required ablation treatment activity for the patient is determined according to the fixed activity method, which is based on clinical and pathological observations and dosimetry methods as well. Two dosimetry approaches are used for the RAI treatment. 8 The first one, defined by Benua et al. 9 in 1962, is to give maximum safe activity to patients. As stated in their study, they aimed to give maximum activity without exceeding 2 Gy dose to the blood as a surrogate for the bone marrow, the critical organ in RAI treatment. The second dosimetry technique is lesion-based dosimetry, which was first mentioned in the study of Maxon et al. in 1983. 10 In their work, they suggested that minimum 300 Gy to the remnant thyroid tissue and minimum 80 Gy to metastases should be given for a successful treatment. The most important advantage of this method was to ablate the remnant tissue with lower activities.
This study aimed to determine the absorbed dose to bone marrow and remnant thyroid tissue of the patients with Differentiated Thyroid Carcinoma before the ablation therapy without interrupting the clinical routine. The associated relative secondary cancer risk was also analyzed. where A 0 is the administered activity, s is the time-integrated activity coefficient (TIAC) (formerly known as residence time), and wt is patient's body weight. Bone marrow dose calculation equation given in the guideline is:

| MATERIALS AND METHODS
To calculate the activity in the blood, 2 ml blood samples at 2, 24, 72, and 120 h were analyzed using the calibrated well-type NaI gamma counter (Capintec Captus-3000, Capintec, Inc. NJ, USA).
Anterior and posterior whole-body counts at 2, 24, 72, and 120 h were measured using the NaI probe detector (Capintec Captus-3000, Capintec, Inc. NJ, USA) at a distance of 2 m from the patient. The probe was positioned at the bottom level of the patient's sternum. 13 The position of the probe and the patient was constant for the counting repeatability.
Whole-body counts at 2 h were taken as a reference that represent the total administered activity because the patients were not allowed micturition until the measurements were performed. Position changes of the activity in the body were ignored.
The TIACs were calculated using the software solution NUK-FIT, 14 choosing the optimal fit functions as proposed by the code. A systematic error in activity determination of 10% was assumed in the calculations.
Another bone marrow dose calculation was performed according to the EANM bone marrow dosimetry guideline (EANM-2010). 15 For thyroid treatment with 131 I-NaI, only the dose from extracellular fluid to bone marrow and dose from the rest of the body to bone marrow were calculated as mentioned in the guideline. To estimate activity concentration in bone marrow based on activity concentration in blood, red marrow-to-blood activity concentration ratio (RMBLR) was used as unity. 15 S factor for the rest of the body was calculated according to EANM-2010. 15 Cristy and Eckerman's 16 10-year-old child, adult female and male MIRD phantoms were used. S factors for bone marrow to bone marrow and whole-body to bone marrow were taken from the study by Stabin and Siegel. 17

2.B | Remnant thyroid tissue dose calculation
For the calculation of dose to remnant thyroid tissue, the Unit-density Sphere Model was used. 18 In this model, the tissues were simulated as spheres with density of 1 g/cm 3 .
The remnant tissue volumes were determined using both Ultrasound (US) and planar gamma camera images taken at 24 h after 131 I intake. In US imaging, the diameters of the remnant tissue were To calculate the cumulative activity in the thyroid, uptake values at 2, 24, 72, and 120 h after injection were determined using the thyroid uptake system. The time-activity curve of the thyroid was integrated using a trapezoidal integration. After the last time point, only the physical decay was taken into account.
The S factors for the remnant tissue dosimetry were determined from the fit function of the data by Stabin and Konijnenberg. 18

2.C | Relative secondary cancer risk assessment in dosimetry approaches
Relative secondary cancer risk assessments in dosimetry approaches were done considering that doses to organs were directly proportional to the administered activity, and relative secondary cancer risk was directly proportional to the organ doses within the same patient.
Thus, relative secondary cancer risk in dosimetry approaches was determined by dividing activity calculated in the dosimetry approach by the applied treatment activity.

| RESULTS
All patients were in stage 1 according to TNM. 19  Blood and bone marrow doses according to the two different EANM guidelines are given in Table 2. There was no significant difference observed between bone marrow doses according to two EANM guidelines (P > 0.05). Significant differences were found between blood and bone marrow doses from both guidelines (P < 0.05).
Effective half-life of the activity was determined as 12.9 h for the total body and 9.6 h for the blood. The corresponding TIAC values were 39.1 and 4.0 h, respectively.
As for thyroid remnant tissue, 24th-hour uptake, effective halflife (T ½ ), and TIAC values are shown in Table 3.
Thyroid tissue volumes measured both with gamma camera and US and their related doses are indicated in Table 4. The volume values were in a wide range between two modalities (average 4.6 cm 3 with gamma camera, while 1.4 cm 3 with US).
To be used in dosimetry calculations for future patients, the correlation between 24-h uptake and TIAC values was also investigated.
Relative secondary cancer risk in selected dosimetry approaches with respect to the applied therapy is given in Blood dose from EANM-2008 (12) (Gy/GBq) Bone marrow dose from EANM-2008 (12) (Gy/GBq) Bone marrow dose from EANM-2010 (15) (Gy/GBq) reduced to approximately one third of the applied therapy by performing lesion-based dosimetry. As the survival rates after well-differentiated thyroid cancer are high, secondary cancer risk due to the radioiodine therapy is an important concern. For this reason, performing remnant tissue dosimetry for ablation treatment of thyroid cancer is strongly recommended.

| CONCLUSION
In the study, the dosimetry approaches in ablation treatment of welldifferentiated thyroid cancer were evaluated. It is shown that activities determined based on fixed activity treatment method can be safely given without reaching the toxic dose for bone marrow.
Administration of maximum safe activities according to the bone marrow dosimetry is not recommended for ablation treatment. On the other hand, with the lesion-based dosimetry, lower activities compared to fixed activity treatment method can be given to ablate the remnant tissue successfully. In addition to this, applying therapy according to lesion-based dosimetry with lower activities decrease the relative secondary cancer risk approximately three times. Large dose differences between patients show the necessity of patientspecific dosimetry.

CONF LICT OF I NTEREST
No conflicts of interest.