Patient organ dose assessment during radioactive iodine treatments of benign thyroid diseases

Abstract

Radioactive iodine is commonly used to treat thyroid benign cases and differentiated thyroid tumors. Two approaches are used in the treatment: fixed and calculated activities. In the fixed activity approach, iodine doses are given based on medical indications, while the calculated approach requires proper dosimetry.

Methods

This study was conducted at Mount Lebanon University Hospital Medical Center (MLHUMC), and included all radioactive iodine treated patients over a period of five consecutive years. The study examined the distribution of patients in terms of gender, age and the administered activities during treatment. Additionally, organ doses were calculated for seven different administered activities using IDAC-Iodine software, specifically for the treatment of benign thyroid cases. Doses were calculated for both female and male patients.

Results

The results revealed higher effective, and organ absorbed doses in female when compared to male patients. Particularly high absorbed doses were observed for thymus, salivary glands, endotracheal region, esophagus, lymphatic nodes. Ratios for organ dose per administered activity were calculated and compared to those from the International Commission on Radiological Protection (ICRP).

Conclusion

These ratios can be used to estimate organ doses in clinical practice and reduce the organ dose with a good clinical outcome.

Implications for practice

This study highlights the value of using personalized dosimetry in iodine-131 treatments to optimize therapeutic effectiveness. Estimating organ-specific doses, especially in female patients, can help reduce radiation exposure to sensitive tissues while maintaining clinical outcomes.

Introduction

Radioactive iodine is widely used for the treatment of thyroid malfunctions and the thyroid cancers. This treatment is associated with radiation induced risks, and therefore administered activities should be calculated for every patient alone. However, according to an internal survey conducted with six physicians at MLHUMC, the current approach to radiation protection of patients undergoing radioactive iodine treatment is not fully optimized. The survey revealed that the administered doses, in most of cases, are fixed and solely determined by the individual patient’s case, without considering important factors such as age, gender, thyroid uptake, weight, or any other factors that could potentially reduce radiation exposure of patients. These assessments are crucial for treatment planning, enabling the customization of the administered dose to minimize radiation exposure to non-targeted organs. Additionally, in the majority of the Lebanese health facilities, patient dosimetry, including the evaluation of the absorbed dose in critical organs like the thyroid, salivary glands, and surrounding tissues is not routinely conducted (66.6 % of the surveyed physicians use fixed doses).

The goal of dosimetry is to determine the appropriate amount of radioactive iodine that will result in therapeutic success in the target volume while minimizing radiation exposure to other organs and tissues, following the “as Low as Reasonably Achievable” principle

The aim of this study is to analyze and evaluate the administered activity levels in patients who received treatment for thyroid conditions at MLHUMC between 2017 and 2022. Additionally, the study aims to estimate the organ absorbed doses received by patients treated with radioactive iodine for benign thyroid diseases at a reference university hospital in Lebanon. Based on the results, recommendations were proposed to optimize the administered activity to improve the treatment outcomes and reduce the potential radiation risks

Methods

Study approval and ethical considerations

Ethical approval was obtained from the appropriate institutional ethics committee (HOP-2023-002).

Data collection

Data from 403 patients treated with radioactive iodine at MLHUMC between January 2017 and December 2023 were collected using an Excel sheet and analyzed by the first author of this study. Patient-specific information, such as age, gender, treating physician, nuclear medicine physician, administered radioactive iodine activity and date of the treatment was recorded. The cohort encompassed patients with a wide spectrum of thyroid conditions, ranging from grave diseases to advanced stages of thyroid cancer.

The IDAC-Iodide software

The IDAC-Iodide software (Internal Dose Assessment by Computer) was used to calculate patient organ-specific absorbed doses. For this study, we used the 2021 release of IDAC-Iodide, as described in reference, which was the latest available version at the time of data processing. This software integrates both the European Association of Nuclear Medicine (EANM) method and the ICRP model, providing enhanced patient specific dosimetry for the thyroid, as well as an estimation of absorbed doses to non-target organs and tissues. The software is capable of calculating absorbed doses for a range of organs and tissues including the adrenals, brain, breast, colon wall, endosteum, endo tracheal region, eye lenses, gallbladder wall, heart wall, kidneys, liver, lung, lymphatic nodes, muscle, esophagus, oral mucosa, ovaries, pancreas, pituitary gland, prostate, read bone marrow, salivary glands, small intestine walls, skin, spleen, stomach wall, testis, thymus, thyroid, tonsil, urinary bladder wall, ureters and uterus/cervix. Organ absorbed doses are calculated according to the ICRP Publication 130 and the specific absorbed fractions of the ICRP Publication 133.

The software supports dose calculations for iodine administered either intravenously or orally. The biokinetic fitting and dosimetric calculations can be customized for the 22 different iodine isotopes.

The mean absorbed dose to a target region is calculated according to the following equation:

where is the time dependent activity at time in a source region , from time of administration to and is the mean absorbed dose in the target region per nuclear transformations in the source region .

is calculated using a radionuclide decay scheme and Monte Carlo simulations of specific absorbed fractions, considering every possible source–target combination. This is expressed as:

Where represents the absorbed fraction from the source region to the target region, divided by the mass of the target region in kilograms of the ith components in the decay scheme and Δ is the energy yield, calculated as:

where is the yield and is the mean energy of the ith transition of radionuclide, expressed in Joule.

The IDAC-Iodide software was also used to calculate the effective dose based on ICRP 103 and ICRP 60 tissue weighting factors. An additional calculation of the effective dose can be performed by the software by assigning a tissue weighting factor equal to zero to the thyroid, acknowledging that radioiodine treatment specifically targets and destroys thyroid cells. This adjustment helps generate a risk indicator for radiation exposure to non-target organs and tissues, providing valuable information regarding potential radiation risks associated with the treatment.

The software also provides the time integrated activity of the thyroid representing the total number of disintegrations per unit time in the thyroid. The absorbed dose calculated can be electron dose, photon dose or the total absorbed dose.

Organ and effective dose calculations are performed by the software by using ICRP adult voxel phantoms, which are computational models representing the human body. Thus, the thyroid masses used in these calculations are 23.4 g for males and 19.5 g for females, though mass corrections can be applied for deviations from these standards.

Organ absorbed dose and effective dose calculation

The most commonly used administered activities for the treatment of benign thyroid diseases within the previously collected patient sample at MLHUMC were 370, 440, 555, 740, 925, 1110, and 1295 MBq. The IDAC-Iodide software was used to calculate the absorbed doses for 33 organs and tissues, including the thyroid, as well as the effective dose for female and male patients. At MLHUMC, administered activities below 1850 MBq were routinely employed for these treatments.

The dose calculations were based on gender-specific models and the assumption that the administered activities corresponded to standard values for female and male patients.

Patient-specific information such as administered activity, gender and iodine uptake was processed using the software. Standard thyroid weights were used in all calculations. In addition, the absorbed dose per 1 MBq of administered activity was determined by dividing the calculated absorbed dose for each organ by the corresponding administered activity. These values were compared to previous studies performed worldwide.

Results

The study population consisted of 403 patients with an uneven gender distribution: 140 (35%) males and 263 (65%) females (cf. Fig. 1). Less than 1.3% of the sample population were between 18 and 20 years old and 82.38% were between 40 and 79 years old (cf Fig. 2), while 12.66% were between 20 and 39 years old.

Figure 1. Gender distribution of the sample population.

Figure 2. Age distribution of the sample population.

Fig. 4 describes the distribution of administered activities given to the patients in milliCuries. Administered activities ranged from 10 mCi (370 MBq) for patients with Grave disease to 200 mCi (7400 MBq) for those with Differentiated Thyroid Carcinoma (DTC). Approximatively 13 % of patients received 20 mCi (740 MBq), 21 % received 30 mCi (1110 MBq) and 22 % received 100 mCi (3700 MBq). Also 6.20 % received 150 mCi (5550 MBq).

To better understand treatment patterns, the administered activities were further segregated into two categories: below 50 mCi and 50 mCi and above. This segregation was used to differentiate between treatments for benign thyroid conditions from those for malignant thyroid diseases based on the data collected. The analysis revealed that 37 % of treatments were for thyroid tumors while the remaining 63 % were for benign thyroid conditions (cf. Fig. 3).

Figure 3. Administered activity distribution by type of thyroid disease.

Figure 4. Distribution of administered radioactive iodine activities for patients treated at MLHUMC.

Table 1 shows the effective doses calculated using the IDAC-Iodide software according to the ICRP 60, and the ICRP103, for the seven fixed administered activities separately, for female and male patients, respectively.

Table 1. Effective dose calculation for seven different administered activities for female and male patients according to ICRP 60 and ICRP 103 tissue weighting factors.

As expected, the effective doses increased proportionally with higher administered activities for both gender when calculated according to both ICRP 60 and ICRP 103. Notably, the effective doses were consistently higher when calculated according to ICRP 60 than ICRP 103 for both genders and for all the administered radioiodine activities. This discrepancy can be attributed to the utilization of lower tissue weighting factors for the thyroid, bladder, gonads, breast, liver, oesophagus, remainder organs in the ICRP 103, particularly for the thyroid.

Additionally, for the same administered activity of radioactive iodine, the effective dose was higher in females compared to male patients. This was attributed to the higher absorbed doses in female patients, which is consistent across both the ICRP 60 and ICRP 103 calculations.

Figure 5, Figure 6 show the organ absorbed dose distribution for seven different administered activities in female and male patients, respectively. As expected, the absorbed doses for all organs increased with higher administered activities for both genders. Among all organs, the thyroid consistently received the highest dose due to its ability to accumulate iodine. Neighboring organs, including the thymus, esophagus, oral mucosa, lymphatic nodes, salivary glands and endotracheal region also received higher doses compared to the remaining organs due to their proximity to the thyroid and the accumulation of radioactive iodine.

Figure 5. Organ absorbed doses (in mGy) distributions for female patients at seven administered activities.

Figure 6. Organ absorbed doses (in mGy) distributions for male patients at seven administered activities.

Fig. 7 shows the average absorbed doses for various organs in female and male patients undergoing radioactive iodine treatment for benign thyroid disease. The data shows that the thyroid average absorbed dose was higher in female patients, with an average of 341 Gy compared to 284 Gy in male patients. Similarly, other organs such as endotracheal region, breast, and salivary glands also received higher average doses in female patients. The main reason is the smaller thyroid weight in female patients, resulting in higher absorbed doses for the thyroid and other organs.

Figure 7. Comparison of average absorbed doses for different organs (mGy) for female and male patients treated for benign thyroid diseases.

Anderson and Mattsson calculated the organ absorbed doses per MBq of administered iodine activity which are presented in Table 2. The average thyroid dose in their study ranged from 390 to 981 mGy per MBq.

Table 2. Female absorbed doses and effective doses in mGy per MBq of administered iodine taken from the study of Anderson and Mattsson.

Table 3 shows the absorbed dose per administered activities calculated by the ICRP, and published on the US Federal and Drug Administration (FDA) website. The Table illustrates the absorbed doses for different thyroid uptakes. The thyroid absorbed doses range from 72 mGy/MBq for an uptake of 5 % and 360 mGy/MBq for an uptake of 25 %. Higher ratios were found in this study ranging between 364 and 439 mGy/MBq (cf. Table 5, Table 6). This difference may be attributed to the higher thyroid uptake observed in cases of hyperthyroidism, which can reach up to 30 % or even higher. The ratios for stomach wall and urinary bladder were slightly higher in the ICRP calculations compared to this study. According to ICRP, the absorbed doses range between 0.45 and 1.7 mGy/MBq for the stomach wall, while a range of 0.35–0.36 mGy/MBq was calculated in this study (cf. Table 6). As for the urinary bladder, ICRP indicated absorbed doses ranging between 0.58 and 1.7 mGy/MBq compared to 0.08 and 0.09 mGy/MBq in the study (cf. Table 6). Table 3 might be used for a fast calculation of organ absorbed doses specially to prevent the stochastic effects for gonads and redbone marrow.

Table 3. Absorbed doses in mGy per MBq of administered iodine according to ICRP.

Table 4 represent the organ absorbed dose, for male and female patients. This ratio can be used for the calculation of organ absorbed dose for any administered activity level.

Table 4. Organ absorbed dose for female male and patients for seven administered activities.

Table 5. Organ average absorbed dose (mGy/MBq) of administered activity for male patients.

Table 6. Organ average absorbed dose (mGy/MBq) of administered activity for female patients.

Discussion

This study focused on organ absorbed doses in individuals undergoing radioactive iodine treatment for benign thyroid diseases. The research was conducted at MLHUMC, with data collected between January 2017 and December 2022.

Findings

The study findings indicated that effective doses and organ absorbed doses for female patients were higher compared to those for male patients. Among all the organs, the thyroid received the highest dose, followed by the thymus, esophagus, oral mucosa, lymphatic nodes, salivary glands and endotracheal region which also received a dose higher than the remaining organs. The absorbed dose per MBq of administered activity was calculated in this study and can be used to estimate the organ absorbed dose based on the administered activity.

Although the calculated doses did not reflect the individualized dose, estimations of the organ absorbed doses based on the administrated activity were provided. However, estimating the organ absorbed dose for the DTC is not straightforward, as it requires considering numerous parameters rather than relying on simple calculations.

Factors influencing dose disparities

Organ doses differed between males and females patients due to the thyroid dose and other physiological factors, highest dose was calculated for the endotracheal region (the region close to the thyroid). These findings indicate that female patients may be exposed to elevated organ absorbed doses compared to male patients, even when receiving treatment for the same medical indication.

In comparison with Anderson and Mattsson the female doses calculated in this study ranged between 437 and 439 mGy per MBq (cf. Table 6). This difference is mainly because of the difference in thyroid uptakes. For stomach wall, the absorbed dose per MBq in this study was equal to 0.36 mGy/MBq (cf. Table 6). In the study of Anderson, the range of the absorbed dose per MBq for the stomach was between 0.32 and 0.56 mGy/MBq (cf. Table 2). The kidney absorbed dose per MBq calculated within this study (0.22 mGy/MBq) (cf. Table 6) was lower than the range reported in Anderson’s study (0.16-1.99 mGy/MBq) (cf. Table 2). Urinary bladder wall and ureter absorbed dose values were slightly lower in our study compared to the values reported by Anderson and Mattsson: 0.09 mGy/MBq for the urinary bladder wall (cf. Table 6) compared to 0.12-0.23 mGy/MBq (cf. Table 2), and 0.05 mGy/MBq for the ureters (cf. Table 6) compared to 0.06-0.24 mGy/MBq (cf. Table 2).

Treatment planning considerations

Thyroid cancer patients might be subject to repetitive high activities. To optimize the radiation protection for non-target organs, adequate planning of target volume exposure is necessary. According to the Council Directive2013/59 Euratom: “for all medical exposure of individuals for radiotherapeutic purposes … exposures of target volume should be individually planned, taking into account that doses of non-target volumes and tissues shall be as low as reasonably achievable and consistent with the intended radiotherapeutic purpose of the exposure”. For patients treated with internal radiation, patient dosimetry plays a crucial role in radiation risk assessment. “Measurement of dose biodistribution and biokinetic for different organs is necessary for the theranostic and other radiopharmaceutical to ensure the safety of the procedures and develop techniques aiming to prevent unnecessary radiation exposure to sensitive organs.

Estimation of tumor dose rates will help to determine the curative or palliative intent of the therapy

Dosimetry for thyroid carcinoma cases is more complicated compared to benign diseases. Software like HERMES Voxel, SurePlan-MRT, HERMES Organ and QDose can be used for dosimetry. Dosimetry can be based on scintigraphy imaging through the injection of I-123 or a small dose of I-131. Alternatively, if available, PET-CT with I-124 can be used. Blood dosimetry can also be applied after the injection of a small dose of I-131. Finally, for patients subject to repetitive treatments, blood dosimetry can be performed during treatment in addition to organ counting. The results obtained from dosimetry will be considered in subsequent treatments (multinodular goiter, grave disease, toxic nodule, etc.)

In the case of benign thyroid diseases, patient dosimetry is relatively easier: the EANM suggested the guidelines via the dosimetry committee on how to perform dosimetry.15, 16, 17 Another method to calculate the treatment dose can be via the IDAC-Iodine software, which allows retrospective estimation of the organ doses. The ICRP has developed a table for absorbed dose per organ per administrative activity, including the thyroid, enabling the treating physicians to estimate the appropriate activity to be administered.

Individualized dosimetry for patients increases the efficacy of radioactive treatment, while reducing the dose of non-target organs. Patient dosimetry requires significant effort and preparation and needs to be performed by a medical physicist; however simpler methods have been discussed for the benign thyroid cases and can be applied easily.

Dosimetry has clinical benefits in the treatment of benign and malignant thyroid diseases. The treatment planning will reduce the effective organ dose, thus optimizing radiation protection for the patient and reducing the stochastic effects.

Thymus and salivary glands

Low doses of radiation can accelerate the thymus aging, where “thymopoiesis decreased relative to non-exposed controls evident years after exposure”Also studies show that high doses of radioactive iodine can cause the dysfunction of salivary glands

Cancer

RAI (Radioactive Iodine) treatments can increase the risk of second primary malignancy especially in the case of doses exceeding 150 mCi.

Greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer.

Study limitation

The study is subject to many limitations particularly regarding cases of Benign Thyroid Diseases. In this study, the organ absorbed doses were calculated via the IDAC-Iodine software. However, several parameters were not included. Firstly, the uptake was not calculated for all patients; only a few received a pretreatment dose. Secondly, the uptake was measured only once, preventing the calculation of organ dose based on the specific uptake. Thirdly, the study was limited to MLHUMC, and a more diverse sample including medical physicians from different medical schools would provide a better understanding of practices in MLHUMC. Fourthly, the thyroid weight was kept standard, as per ICRP adult voxel phantoms, and not tailored to each individual. These factors should be taken into consideration when discussing the results obtained, also should be taken into consideration in further studies to clarify the procedures and rules followed in Lebanon regarding radioactive treatments.

Regarding cases of thyroid differentiated cancer. The organ dose estimation is different between patients due to the need for individualized treatment. Thus, calculations should be made via dedicated software for each patient. The IDAC-Iodine software used in this study is only applicable for benign thyroid cases and cannot be utilized for thyroid cancer cases. Also, all treatments administered in this study were based on standard fixed activities.

Conclusion

In conclusion, it is crucial to foster collaboration between the regulatory authority and professional committees at the national level to implement patient dosimetry within the Lebanese Nuclear Medicine department. This collaborative effort will help ensure the effective implementation of dosimetry practices and enhance the overall quality of patient care in nuclear medicine. Future studies should explore the best plans for a curative treatment with the lowest administrated dose that fits with the Middle East population taking into consideration the difference between genders and thyroid weight.

Ethics approval and consent to participate

Ethical approval for this study was obtained from the institutional review board of Mount Lebanon University Hospital Medical Center under the code MLH: HOP-2023-002. Due to the retrospective design of the study, the anonymous nature of the collected data and the absence of any impact on the clinical care of the patients, patient informed consent was not required.

Availability of data

Data required for this study may be made available by the author(s) upon reasonable request.

Author contribution statement

EI: Writing- Original Draft preparation, Conceptualisation, Methodology, Investigation, Data curation.

CR: Supervision, Visualisation, Investigation, Writing, Reviewing and Editing, Conceptualisation, Methodology.

MS: Writing- Reviewing and Editing, Conceptualisation.

MM: Writing- Reviewing and Editing, Validation.

ED: Writing- Reviewing and Editing, Validation.

EG: Writing- Reviewing and Editing, Validation.

DE: Writing- Reviewing and Editing, Conceptualisation, Methodology.

CM: Supervision, Visualisation, Investigation, Writing, Reviewing and Editing, Conceptualisation, Methodology.

Declaration of Generative AI and AI-assisted technologies in the writing process

The results presented in this paper, including the writing of the manuscript, were obtained without the use of artificial intelligence for data generation, analysis, or text generation.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest statement

None.

Acknowledgments

Not applicable.