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Accueil Tous les numéros Volume 60 / Numéro 3 (Juillet-Septembre 2025) Radioprotection, 60 3 (2025) 277-284 Full HTML
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Numéro
Radioprotection
Volume 60, Numéro 3, Juillet-Septembre 2025
Page(s) 277 - 284
DOI https://doi.org/10.1051/radiopro/2025005
Publié en ligne 15 septembre 2025

© M. Jabari, Published by EDP Sciences 2025

Licence Creative CommonsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1 Introduction

Peptide receptor radionuclide therapy (PRRT) is an important class of systemic treatment of patients with unrespectable or metastasized neuro-endocrine tumors (NETs). Radiolabeled somatostatin analogs such 177Lu-DOTATATE (DOTA is 1,4,7,10-tetraazadodecane-N,N_,N_,N_-tetraacetic acid) and 90 Y-DOTATATE are most successful in detecting, imaging and therapy of tumors expressing somatostatin receptors (Mittra, 2018; Delpassand et al., 2014). Localization of these radiopharmaceuticals after ligand binding makes them a favorable target for therapy (Sandström et al., 2018; Lassmann et al., 2021). Radiolabeled peptides are excreted mainly via the kidneys and are partly reabsorbed in the proximal tubular cells. Therefore retention and excretion of these molecules from urine pathway may cause toxicity due to highbsorbed dose to critical organs such as kidney, liver and bladder. This toxicity precludes the use of higher doses, thus limiting the efficacy of therapy.

Internal dosimetry is an outstanding procedure in nuclear medicine to optimize both diagnostic and therapeutic procedures (Carneiro et al., 2015; Potter, 2024) and the resulting dose to the patient (Bertho and Bourguignon, 2024). Pre-estimation of absorbed dose in critical target organs can be performed by atlas-based simulations using advanced anthropomorphic phantoms and Monte Carlo codes (Panta, et al. 2012). The ICRP developed reference computational phantoms in mesh format to provide anatomically more realistic representations of the human body. These advanced phantoms define numerous source and target regions with different size (mass and height) providing more similarity to real conditions. Furthermore, the results obtained from dosimetry simulations may help to extract approximate values of absorbed dose in different organs and optimize the selection of radionuclide.

90Y and 177Lu are two commonly used radionuclides in therapy of neuro-endocrine tumors (Seregni et al., 2014; Zemczak et al., 2021). Based on the previous literature, 177Lu and 90Y have low and high energy beta particles, respectively. According to the range of beta particles emitted from each of these two radionuclides, they are widely used for treating smaller and larger tumors (Zweit, 1996; Ljungberg et al., 2016). It is recommended to use the appropriate cocktail of these radionuclides due to different size of metastatic tumors. Another important problem in radionuclide therapy is the prevention of critical organ radiotoxicity. Although a radionuclide may have a high efficacy but high absorbed dose in critical organs close to the target organ makes it an unsuitable selection for therapy (Kunikowska et al., 2011; Huizing et al., 2018). An important factor affecting critical organ dose is the size of that organ, which isdepended on BMI.

There are a few studies that compare the differences between the absorbed doses between 90Y-DOTATATE and 177Lu-DOTATAE (Segars et al., 2017). Most study in this field use simple stylized phantom such as MIRD and do not consider anatomical details of organs (Mattsson, 2015). Human-simulating computational phantoms have become an important tool for dosimetric calculations in medical imaging and radiation therapy. Using these phantom in Monte Carlo simulation can lead to more convenient and also yield reliable results. In this study we used male CRP phantom to perform an accurate estimation of absorbed dose in organs of interest. A primary aim of this work was to assess differences in 177Lu and 90Y- DOTATATE dose coefficient (dose per unit cumulated activity) named S-values estimations using various patient morphologies. S-values of 177Lu and 90Y- DOTATATE in different body mass indexes (BMIs) of ICRP (Pinto et al., 2020) male phantoms were calculated for pre-estimation of absorbed dose in critical target organs using GATE (GEANT4 Application to Tomographic Emission). We then investigated differences due to phantom format by comparing dose coefficients.

2 Materials and methods

All simulations in this study were performed using GATE version 8.2 based on the Geant4 (Geometry And Tracking, version 10.4).

We used the method developed by Segars et al. (2017) to produce six total body ICRP male hantoms with different BMIs. Some parameters of phantom such as BMI are changeable. The reference mass and height are 60 kg and 163 cm respectively (BMI = 22.6 kg/cm2). The adult mesh reference phantoms were reshaped and scaled to culminating in an additional 6 male phantomphantoms representing the 10th, 50th, and 90th percentiles of standing height and weight corresponding to BMI of 23, 24.9, 27.1, 28.4, 29.3, 34.5. The matrix size of each phantom was 128 × 128 × 300 with a voxel size of 3.125 mm × 3.125 mm × 3.125 mm to cover the desired region of the body (Fig. 1). Dosimetry calculations were performed for 20 MBq activity of 177Lu-DOTATATE and 90Y- DOTATATE that were distributed uniformly in each voxels of the source organs.

The detailed decay data and emission spectra of selected radionuclides were taken from MIRD: radionuclide data and decay schemes (Goddu, 1997). For each radionuclide, the emitted energy spectra (gamma, X-ray, beta, internal conversion, Auger electrons and alpha) were considered independently to estimate the relative contribution of each radiation independently. The transitions for each radionuclide are summarized in Table 1.

Simulations were performed by Intel® Core™ i5 Processors with 6 GB RAM. In total, 107 histories were simulated for each phantom. After dosimetry simulations with GATE, the output is two binary files containing the absorbed dose in voxels (in cGy) and the corresponding uncertainties respectively. Using MATLAB (version R2017b), results were converted to numeric values. We chose spine, bladder, kidneys, and salivary glands as the source organs according to the biodistribution of selected radiopharmacuticals and we calculated the S-value (in units of mGy/MBq.s) based on Medical International Radiation Dose (MIRD) committee guideline [13] in kidneys, spleen, liver, and bladder as the target organs. several target regions are defined in the ICRP phantom that comprise multiple sub regions (e.g. kidneys, comprising left and right renal pelvis, cortex, and medulla). The mass weighted combination of absorbed doses (in unit of mGy per MBq.s) were calculated as the mean dose to such regions according to the equation (1).

Smreg=∑rT∈mregM(rT∈mreg)M(mreg)S(rT∈mreg)(1)

where Smreg is the S-value for a multiregional target; M (rT ∈ mreg) is the mass of a region rT comprising the multiregional target; M(mreg) is the total mass of the multiregional target; and S (rT ∈ mreg) is the S-value for a subregion.

In this study, paired t-test and linear regression were used to evaluate the correlation of the interested organ absorbed dose per unit cumulated activity as S-values and BMI. All statistical tests and comparisons were done using SPSS version 18 and SYSTAT 13 software.

thumbnail Fig. 1

ICRP phantom that covers the interested organs.
Table 1

Summery of the decay transition of the radionuclides investigated in this study. The third column to fifth column shows respectively the number of emitted rays, sum of the yield of each ray (∑Yi) and sum of the product of yield and energy divided by total yield ∑Yi.Ei∑Yi named mean energy.

3 Results

Results are presented in Tables 2–7. The S values in both self-absorptions and target organs were lower for 177Lu-DOTATATE as compared to 90Y-DOTATATE. Differences of S- values were not significant (P < 0.005). The highest difference between the absorption is in kidneys (P = 0.0032) when source is in kidney. When the source organ is the kidneys, the greatest S value is 0.0025 from 90Y-DOTATATE and 3.55e-04 from 177Lu-DOTATATE in BMI of 28.3. The highest S-value in BMI of 34.5 in bladder from bladder is 0.01 from90Y-DOTATATE, whereas it is 0.0049 from 177Lu-DOTATAE. The most self-absorption (when source and target are the same) in spine is in BMI of 28.3 and is 7.04e-04 from 90Y-DOTATATE and 1.12e-04 from 177Lu-DOTATAE. For the spleen as source organs’ self-absorption have the S-value (in mGy/MBq.s) of 0.0035 from the source of 90Y-DOTATATE and about 7.5e-04 from 177Lu-DOTATAE in all BMI. Moreover, when liver is considered as the source organ(source is distributed in liver), the absorption in kidneys and bladder is approximately 100 times lower in 177Lu-DOTATAE.. In the case of organs such as liver and pancreas, all the trend lines varied inversely with S-values and they demonstrated a strong or weak tendency to decrease with BMI. Also, plots in Figure 2 illustrate that for 177Lu-DOTATAE, the self-absorption is dramatically lower than that of 90Y-DOTATATE. The dependence of the dose to the morphology of the patient is shown in these figures for the percentile-specific phantoms.. More specifically, all the R2 values were greater than 0.7. For all these results, organ doses decreased with increasing BMI. The S values negatively correlates strongly with body mass index (Spearman r = 0.9505; P < 0.0001).

Table 2

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 23.0 of male ICRP phantom

Table 3

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 24.9 of male ICRP phantom

Table 4

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 27.1 of male ICRP phantom

Table 5

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 28.4 of male ICRP phantom

Table 6

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 29.3 of male ICRP phantom

Table 7

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 34.5 of male ICRP phantom

thumbnail Fig. 2

Relative differences between Lu-177(a) and Y-90(b) absorbed dose in different organs.

4 Discussion

The high interest for dosimetry of 90Y-DOTATATE in clinical researches, necessitate a knowledge on the absorbed dose of organs (Cwikla et al., 2010; Kunikowska et al., 2011; Sowa-Staszczak et al., 2011). But, to the best of our knowledge, there are very few studies that compare the differences between the absorbed doses between 90Y-DOTATATE and 177Lu-DOTATAE. Capala et al. evaluated the dosimetry methods for radiopharmaceutical therapy and stated that the main different feature between 177Lu-DOTATAE and 90Y-DOTATATE is the particles and energy emitted by each disintegration (Capala et al., 2021). Beside this factor, patient specifics such as height, weight, sex, and underlying physical factors (such as linear energy transfer, attenuation) affect S-values. Due to lower energy of beta particles emitted from 90Y as compared to 177Lu and consequently due to the lower range of these particles, the absorbed dose to the organs would be lower. Alnaaimi et al. calculated S-Values (in mGy/MBq s) in some of the critical organs according MIRD formalism and 90Y-DOTATATE and 177Lu-DOTATATE biodistribution (Alnaaimi et al., 2021). They showed that for both target and self-absorption, S-values are notably reduced when 90Y-DOTATATE is substituted by 177Lu-DOTATATE. Their results are in agreement with the trend of our results. Having effective half-life of 177Lu and 90Y, rough estimation of absorbed dose (in Gy) in target organs can be provided for physicians and this also help them to decide how much of activity should be injected according to the patient’s BMI (Veress et al., 2010) and the therapeutic or imaging objectives. Ahmadzadehfar et al. emphasized that DOTATATE-based radiopharmaceuticals is a molecular target with diagnostic and therapeutic agent simultaneously (Ahmadzadehfar et al., 2015), and reported that clinical study with 177Lu-DOTATATE has demonstrated very effective results and was well tolerated. This point comes to more attention in our study when deciding for assessment of absorbed dose ratio for Lu-177 therapy − as a promising new therapeutic agent. The results for different BMIs, demonstrate that using 177Lu-DOTATATE has less hazards compared to 90Y-DOTATATE. Because 177Lu-DOTATATE can detect lesions even more precisely, its lower S-values in target organs pose another reason for bias towards 90Y-DOTATATE. The major drawback of the current study is the lack of simulation with real patient’s data. There are subtle variations between biodistribution of different derivatives of DOTATATE-based ligands. The small differences between various derivatives of DOTATAE-based agents cannot be assessed in phantom studies. This will be of more focus in our future work on real patients. For instance, there is a slight difference between the biodistribution of 177Lu-DOTATATE and 90Y-DOTATATE. The differences include renal clearance of 90Y-DOTATATE that is less than 177Lu-DOTATATE which leads to less accumulation of radiopharmaceutical in bladder, resulting in better capacity of the surrounding bladder and bladder tissue. Also, liver absorption is higher in 90Y-DOTATATE compared to 177Lu-DOTATATE. This high absorption is considered a weakness in detecting liver metastases. Patient-specific dosimetry definitely will help to determine accurately amount of differences between these two tracers. Data gained from real patients imaging may lead also to determine how much total received dose is different for these two agents as well as organ doses.

5 Conclusion

Our results show that the absorbed dose falls down dramatically when 177Lu-DOTATATE is employed instead of 90Y-DOTATATE. The lower absorbed dose in patient body may be another reason to put 177Lu-DOTATATE in superiority for neuroendocrine tumor therapy. As a consequence, patients with a high BMI were exposed to more radiation than those with a low BMI. To prevent excessive dosage to patients, it is important to consider the relationship between body size and dose.

Funding

This article did not receive any specific funding.

Conflicts of interests

The authors report no conflict of interest.

Data availability statement

The author confirms that the data supporting the findings of this study are available within the article.

Ethics approval

Research does not involve human participants or animals Informed consent.

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Cite this article as: Jabari M. 2025. Size-dependent dose estimation applied to 177Lu and 90Y-DOTATATE using ICRP Phantoms. Radioprotection 60(3): 277–284. https://doi.org/10.1051/radiopro/2025005

All Tables

Table 1

Summery of the decay transition of the radionuclides investigated in this study. The third column to fifth column shows respectively the number of emitted rays, sum of the yield of each ray (∑Yi) and sum of the product of yield and energy divided by total yield ∑Yi.Ei∑Yi named mean energy.

In the text
Table 2

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 23.0 of male ICRP phantom

In the text
Table 3

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 24.9 of male ICRP phantom

In the text
Table 4

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 27.1 of male ICRP phantom

In the text
Table 5

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 28.4 of male ICRP phantom

In the text
Table 6

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 29.3 of male ICRP phantom

In the text
Table 7

S-values (mGy/MBq.s) for 177Lu-DOTATATE & 90Y-DOTATATE for BMI 34.5 of male ICRP phantom

In the text

All Figures

thumbnail Fig. 1

ICRP phantom that covers the interested organs.
In the text
thumbnail Fig. 2

Relative differences between Lu-177(a) and Y-90(b) absorbed dose in different organs.
In the text

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