## 4 Discussion  
The purpose of this study was the dosimetric evaluation of Lutathera(r). For the dose calculation, we used GATE for MC simulations and the Planet(r) Dose software from DOSIsoft. The mean absorbed doses for every organ agree with the available literature [16; 29; 41; 42].  
Regarding the comparison between GATE and Planet(r), we observe that the bi-exponential fitting of the TACs presented similar results with GATE. The average relative difference between them is less than 11.1% for every organ (Table 3). The differences can be explained by our limited sample size (n = 15 for spleen and n = 23 for liver and kidneys), the method that the CF was calculated, as well as the difference in the technique of both methods. Planet(r) makes an estimation of dose while considering the TACs, in comparison to GATE, where only one specific time point was considered. Nevertheless, both techniques are an estimation procedure that has a lot of room for improvement.  
An error-prone experimental set up may introduce uncertainties and affect dose calculation. The Bland-Altman plots demonstrate that there is no proportional bias between GATE and Planet(r) (bi-exp), and the mean of the differences is close to zero for all organs. Moreover, we observed that most of the differences (GATE-Planet(r) (bi-exp)) are positive for all organs. This may indicate that the CF has a slightly higher value than the defined. However, the limits of agreement were less than 1 Gy for the spleen and the left and right kidneys, and slightly higher for the liver. On the other hand, the results of the tri-exponential fitting are not satisfactory. The tri-exponential fitting considers an uptake phase, a rapid and a long-term clearance phase, which accurately describes the pharmacokinetics. Despite that, the relative differences between GATE and Planet(r) (tri-exp) are 60.6% and 30.5% for right kidney and spleen, respectively. This indicates that four time points are not enough for tri-exponential fitting. Furthermore, there is a calculated value of absorbed doses that shows a large difference to the mean value, which may be attributed to the small dataset.  
Based on prior knowledge regarding renal absorbed dose tolerance from external beam radiation therapy, the dose limit for kidneys is 23 Gy. In addition, the biologically effective dose (BED) for PRRT with \({}^{177}\)Lu has been estimated to be 40 Gy for patients without risk factors for renal toxicity and 28 Gy for those with risk factors [43]. Figure 6 shows that  
Figure 6: Cumulative absorbed dose per patient for liver, spleen and right and left kidney.  
none of these limits were exceeded. However, we observed that the cumulative absorbed dose indicates significant intra-patients' variations, even though the administrated activity was the same. The aforementioned variations pose the need for patient-specific dosimetry calculation in nuclear medicine therapeutic applications.  
The main limitations of the present study are the small data sample and the lack of dose calculation within lesions. Further studies should be conducted in the future, comparing GATE and Planet(r) Dose (bi-exp), to obtain more robust results.