1. |
- Brolin, Gustav, et al.
(författare)
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Pharmacokinetic digital phantoms for accuracy assessment of image-based dosimetry in (177)Lu-DOTATATE peptide receptor radionuclide therapy.
- 2015
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 60:15, s. 6131-6149
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Tidskriftsartikel (refereegranskat)abstract
- Patient-specific image-based dosimetry is considered to be a useful tool to limit toxicity associated with peptide receptor radionuclide therapy (PRRT). To facilitate the establishment and reliability of absorbed-dose response relationships, it is essential to assess the accuracy of dosimetry in clinically realistic scenarios. To this end, we developed pharmacokinetic digital phantoms corresponding to patients treated with (177)Lu-DOTATATE. Three individual voxel phantoms from the XCAT population were generated and assigned a dynamic activity distribution based on a compartment model for (177)Lu-DOTATATE, designed specifically for this purpose. The compartment model was fitted to time-activity data from 10 patients, primarily acquired using quantitative scintillation camera imaging. S values for all phantom source-target combinations were calculated based on Monte-Carlo simulations. Combining the S values and time-activity curves, reference values of the absorbed dose to the phantom kidneys, liver, spleen, tumours and whole-body were calculated. The phantoms were used in a virtual dosimetry study, using Monte-Carlo simulated gamma-camera images and conventional methods for absorbed-dose calculations. The characteristics of the SPECT and WB planar images were found to well represent those of real patient images, capturing the difficulties present in image-based dosimetry. The phantoms are expected to be useful for further studies and optimisation of clinical dosimetry in (177)Lu PRRT.
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2. |
- Gustafsson, Johan Ruben, et al.
(författare)
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On the biologically effective dose (BED)-using convolution for calculating the effects of repair: I. Analytical considerations.
- 2013
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 58:5, s. 1507-1527
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a new mathematical formulation of biologically effective dose (BED) for radiation therapy where effects of repair need to be considered. The formulation is based on the observation that the effects of repair, both during protracted irradiation and of incomplete repair between fractions, can be written using a convolution, i.e. [Formula: see text] where T is the total irradiation time, R(T)(t) is the absorbed dose rate as a function of time t and I(t) is the function describing repair. To validate this formulation, the previously published expressions for instant and protracted irradiation are first summarized. Then, by analytical derivation, it is shown that the new formulation gives identical results. The calculation of BED can thus be treated within one single mathematical framework, applicable in external beam therapy, brachytherapy, radionuclide therapy, or a combination of these treatment modalities. Moreover, the new formulation allows for a straightforward incorporation of different repair models and has the advantage of being numerically applicable.
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3. |
- Gustafsson, Johan Ruben, et al.
(författare)
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On the biologically effective dose (BED)-using convolution for calculating the effects of repair: II. Numerical considerations.
- 2013
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 58:5, s. 1529-1548
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown analytically that the biologically effective dose (BED), including effects of repair during irradiation and of incomplete repair between fractions, can be formulated using a convolution between the absorbed dose rate function and the function describing repair. In this work, a discrete formalism is derived along with its implementation via the fast Fourier transform. The implementation takes the intrinsic periodicity of the discrete Fourier transform into consideration, as well as possible inconsistencies that may arise due to discretization and truncation of the functions describing the absorbed dose rate and repair. Numerically and analytically calculated BED values are compared for various situations in external beam radiotherapy, brachytherapy and radionuclide therapy, including the use of different repair models. The numerical method is shown to be accurate and versatile since it can be applied to any kind of absorbed dose rate function and allows for the incorporation of different repair models. Typical accuracies for clinically realistic examples are in the order of 10(-3)% to 10(-5)%. The method has thus the potential of being a useful tool for the calculation of BED, also in situations with complicated irradiation patterns or repair functions.
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4. |
- Gustafsson, Johan Ruben, et al.
(författare)
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Uncertainty propagation for SPECT/CT-based renal dosimetry in (177)Lu peptide receptor radionuclide therapy.
- 2015
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 60:21, s. 8329-8346
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Tidskriftsartikel (refereegranskat)abstract
- A computer model of a patient-specific clinical (177)Lu-DOTATATE therapy dosimetry system is constructed and used for investigating the variability of renal absorbed dose and biologically effective dose (BED) estimates. As patient models, three anthropomorphic computer phantoms coupled to a pharmacokinetic model of (177)Lu-DOTATATE are used. Aspects included in the dosimetry-process model are the gamma-camera calibration via measurement of the system sensitivity, selection of imaging time points, generation of mass-density maps from CT, SPECT imaging, volume-of-interest delineation, calculation of absorbed-dose rate via a combination of local energy deposition for electrons and Monte Carlo simulations of photons, curve fitting and integration to absorbed dose and BED. By introducing variabilities in these steps the combined uncertainty in the output quantity is determined. The importance of different sources of uncertainty is assessed by observing the decrease in standard deviation when removing a particular source. The obtained absorbed dose and BED standard deviations are approximately 6% and slightly higher if considering the root mean square error. The most important sources of variability are the compensation for partial volume effects via a recovery coefficient and the gamma-camera calibration via the system sensitivity.
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5. |
- Minguez Gabina, Pablo, et al.
(författare)
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Biologically effective dose in fractionated molecular radiotherapy-application to treatment of neuroblastoma with (131)I-mIBG.
- 2016
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 61:6, s. 2532-2551
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Tidskriftsartikel (refereegranskat)abstract
- In this work, the biologically effective dose (BED) is investigated for fractionated molecular radiotherapy (MRT). A formula for the Lea-Catcheside G-factor is derived which takes the possibility of combinations of sub-lethal damage due to radiation from different administrations of activity into account. In contrast to the previous formula, the new G-factor has an explicit dependence on the time interval between administrations. The BED of tumour and liver is analysed in MRT of neuroblastoma with (131)I-mIBG, following a common two-administration protocol with a mass-based activity prescription. A BED analysis is also made for modified schedules, when due to local regulations there is a maximum permitted activity for each administration. Modifications include both the simplistic approach of delivering this maximum permitted activity in each of the two administrations, and also the introduction of additional administrations while maintaining the protocol-prescribed total activity. For the cases studied with additional (i.e. more than two) administrations, BED of tumour and liver decreases at most 12% and 29%, respectively. The decrease in BED of the tumour is however modest compared to the two-administration schedule using the maximum permitted activity, where the decrease compared to the original schedule is 47%.
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