A stylized computational model of the rat for organ dosimetry in support of preclinical evaluations of peptide receptor radionuclide therapy with (90)Y, (111)In, or (177)Lu (original) (raw)
Related papers
Acta Oncologica, 2011
Background. Clinical treatment with radionuclides is usually preceded by biokinetic and dosimetry studies in small animals. Evaluation of the therapeutic effi cacy is essential and must rely on accurate dosimetry, which in turn must be based on a realistic geometrical model that properly describes the transport of radiation. It is also important to include the source distribution in the dosimetry calculations. Tumours are often implanted subcutaneously in animals, constituting an important additional source of radiation that often is not considered in the dosimetry models. The aims of this study were to calculate S values of the mouse, and determine the absorbed dose contribution to and from subcutaneous tumours inoculated at four different locations. Methods . The Moby computer program generates a three dimensional (3D) voxel-based phantom. Tumours were modelled as half-spheres on the body surface, and the radius was varied to study different tumour masses. The phantoms were used as input for Monte Carlo simulations of absorbed fractions and S factors with the radiation transport code MCNPX 2.6f. Calculations were performed for monoenergetic photons and electrons, and the radionuclides 125 I, 131 I, 111 In, 177 Lu and 90 Y. Results. Electron energy and tumour size are important for both self-and cross-doses. If the activity is non-uniformly distributed within the body, the position of the tumour must be considered in order to calculate the tumour absorbed dose accurately. If the uptake in the tumour is high compared with that in adjacent organs the absorbed dose contribution to organs from the tumour cannot be neglected. Conclusions. In order to perform accurate tumour dosimetry in mouse models it is necessary to take the additional contribution from the activity distribution within the body of the mouse into account. This may be of signifi cance in the interpretation of radiobiological tumour response in pre-clinical studies.
Impact of Mouse Model on Preclinical Dosimetry in Targeted Radionuclide Therapy
Proceedings of the IEEE, 2000
Introduction: Small animal dosimetry serves as an important link in establishing a relationship between absorbed dose and biological effect during pre-clinical targeted radionuclide therapy. Dosimetric approaches reported to date are based on models aiming at representing the animals used during pre-clinical experiments. However, anatomical variations between models may generate differences in the dosimetric results. Our goal was to assess the impact of the mouse model on the absorbed dose per cumulated activity (S value, in Gy per Bq.s). Methodology: Two datasets were considered. The first one was developed in our laboratory and is a voxel-based model of a 30g female nude mouse. Images were segmented manually to identify more than 30 organs and sub-organs. The second dataset originates from the DIGIMOUSE project. In that model, a 28g normal male nude mouse was used to generate the segmented structures of 9 regions in the head and 12 major organs. A software developed in our laboratory allowed us to read each 3D mouse atlas slice by slice, to crop the mouse volume to remove background air voxels, and to write the geometry description as an input file for the Monte-Carlo code MCNPX using "repeated structure representation". A linear interpolation scales the voxel size as a function of the total body mass. Results: The comparison of various voxel-based mouse dosimetric models shows that even when scaled to the same total-body mass, models from different mouse breed or gender demonstrate very different organ masses, volumes, and therefore S values. Conclusions: Computation of the S values for pre-clinical studies depends strongly on the definition of the mouse model. Our computational model is a step in the direction of a more realistic description of the geometry in pre-clinical dosimetry. 3/3
2007
Phantom-based and patient-specific imaging-based dosimetry methodologies have traditionally yielded mean organ absorbed doses or spatial dose distributions over tumors and normal organs. In this work, radiobiological modeling is introduced to convert the spatial distribution of absorbed dose into biologically effective dose and equivalent uniform dose parameters. The methodology is illustrated using data from a thyroid cancer patient treated with radioiodine. METHODS: Three registered SPECT/CT scans were used to generate 3-D images of radionuclide kinetics (clearance rate) and cumulated activity. The cumulated activity image and corresponding CT were provided as input into an EGSnrc-based Monte Carlo calculation; the cumulated activity image defined the distribution of decays while an attenuation image derived from CT was used to define the corresponding spatial tissue density and composition distribution. The rate images were used to convert the spatial absorbed dose distribution to a Biologically Effective Dose (BED) distribution which was then used to estimate a single Equivalent Uniform Dose (EUD) for segmented volumes of interest. EUD was also calculated from the absorbed dose distribution directly. RESULTS: Validation using simple models and also comparison of the dose-volume histogram to a previously analyzed clinical case is shown as well as the mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for an illustrative clinical case of a pediatric thyroid cancer patient with diffuse lung metastases. The mean absorbed dose, mean BED and EUD for tumor was 57.7, 58.5 and 25.0 Gy, respectively. Corresponding values for normal lung tissue were 9.5, 9.8 and 8.3 Gy, respectively. CONCLUSION The analysis demonstrates the impact of radiobiological modeling on response prediction. The 57% reduction in the equivalent dose value for the tumor reflects a high level of dose non-uniformity in the tumor and a corresponding reduced likelihood of achieving a tumor response. Such analyses are expected to be useful in treatment planning for radionuclide therapy.
Voxel-based mouse and rat models for internal dose calculations
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2006
The ability to estimate absorbed doses in experimental animals to which radiolabeled material has been administered may be important in explaining and controlling potential radiation toxicity observed during preclinical trials. Most previously reported models for establishing doses to small animals have been stylized and mathematically based. This study establishes dose factors for internal sources in realistic models of a typical mouse and a typical rat, based on image data obtained using a dedicated small-animal CT scanner. A transgenic mouse (body mass, 27 g) and a Sprague-Dawley rat (body mass, 248 g) were imaged using the dedicated small-animal CT scanner. Identified organs were segmented using computer tools that Vanderbilt University applies to process human images for 3-dimensional dosimetry. Monte Carlo N-particle transport code (MCNP) input files were prepared from the 3-dimensional, voxel-based image data. Using methods established for human studies, radiation transport c...
Journal of Nuclear Medicine, 2007
Phantom-based and patient-specific imaging-based dosimetry methodologies have traditionally yielded mean organ-absorbed doses or spatial dose distributions over tumors and normal organs. In this work, radiobiologic modeling is introduced to convert the spatial distribution of absorbed dose into biologically effective dose and equivalent uniform dose parameters. The methodology is illustrated using data from a thyroid cancer patient treated with radioiodine. Methods: Three registered SPECT/CT scans were used to generate 3-dimensional images of radionuclide kinetics (clearance rate) and cumulated activity. The cumulated activity image and corresponding CT scan were provided as input into an EGSnrc-based Monte Carlo calculation: The cumulated activity image was used to define the distribution of decays, and an attenuation image derived from CT was used to define the corresponding spatial tissue density and composition distribution. The rate images were used to convert the spatial absorbed dose distribution to a biologically effective dose distribution, which was then used to estimate a single equivalent uniform dose for segmented volumes of interest. Equivalent uniform dose was also calculated from the absorbed dose distribution directly. Results: We validate the method using simple models; compare the dose-volume histogram with a previously analyzed clinical case; and give the mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for an illustrative case of a pediatric thyroid cancer patient with diffuse lung metastases. The mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for the tumor were 57.7, 58.5, and 25.0 Gy, respectively. Corresponding values for normal lung tissue were 9.5, 9.8, and 8.3 Gy, respectively. Conclusion: The analysis demonstrates the impact of radiobiologic modeling on response prediction. The 57% reduction in the equivalent dose value for the tumor reflects a high level of dose nonuniformity in the tumor and a corresponding reduced likelihood of achieving a tumor response. Such analyses are expected to be useful in treatment planning for radionuclide therapy.
Research Square (Research Square), 2022
Purpose: To develop a model of the internal vasculature of the adult liver for blood dosimetry in radiation therapy and demonstrate its application to differentiation of radiopharmaceutical decay sites within liver parenchyma separate from those within the organ's blood content. Method: Computer-generated models of hepatic arterial (HA), hepatic venous (HV), and hepatic portal venous (HPV) vascular trees were created within individual lobe segments of the ICRP adult female and male livers (AFL/AML) via an in-house algorithm based. Hemodynamic and geometric parameters of the main vessels were used as inputs. For each iteration of the algorithm, pressure, blood flow, and vessel radii within each tree were updated as each new vessel was created and connected to the viable bifurcation site. The vascular networks created inside the AFL/AML were then tetrahedralized to coupling to PHITS. Specific Absorbed Fractions (SAF) were computed for monoenergetic alpha particles, electrons, and photons. Dual-region liver models of the AFL/AML were proposed and particle-specific SAF values were computed assuming blood decays as modeled in two regions: (1) sites within explicitly modeled hepatic vessels, and (2) sites within the hepatic blood pool residing outside these vessels to include the liver capillaries and blood sinuses. S-values for 22 radionuclides commonly used in radiopharmaceutical therapy were computed using the dual-region liver models and compared to S-values obtained in a single-region liver model of homogenized liver parenchyma (LP) and liver blood (LB). Results: Liver models with virtual vasculatures of ~6000 non-intersecting straight cylinders representing the HA, HPV, and HV circulations were created for the ICRP reference AFL and AML. SAF energy profiles were obtained using the single-region and dual-region models. For alpha emitting radionuclides, S-values using the single-region models were approximately 14% and 11% higher than the S-values obtained using the dual-region AFL and AML models, respectively. For beta and auger-electron emitters, S-values based on the single-region model were up to 13% and 11% higher than in the dual-region model for the AFL and AML , respectively. Conclusions: The methodology employed for the liver can be applied to all major organs of the computational phantom for both improved dosimetry of organ parenchyma.
Radioprotection, 2014
For targeted radionuclide therapies, treatment planning usually consists of the administration of standard activities without accounting for the patient-specific activity distribution, pharmacokinetics and dosimetry to organs at risk. The OEDIPE software is a user-friendly interface which has an automation level suitable for performing personalized Monte Carlo 3D dosimetry for diagnostic and therapeutic radionuclide administrations. Mean absorbed doses to regions of interest (ROIs), isodose curves superimposed on a personalized anatomical model of the patient and dosevolume histograms can be extracted from the absorbed dose 3D distribution. Moreover, to account for the differences in radiosensitivity between tumoral and healthy tissues, additional functionalities have been implemented to calculate the 3D distribution of the biologically effective dose (BED), mean BEDs to ROIs, isoBED curves and BED-volume histograms along with the Equivalent Uniform Biologically Effective Dose (EUD) to ROIs. Finally, optimization tools are available for treatment planning optimization using either the absorbed dose or BED distributions. These tools enable one to calculate the maximal injectable activity which meets tolerance criteria to organs at risk for a chosen fractionation protocol. This paper describes the functionalities available in the latest version of the OEDIPE software to perform personalized Monte Carlo dosimetry and treatment planning optimization in targeted radionuclide therapies.
Journal of Nuclear Medicine, 2010
Accurate dosimetry in 90 Y peptide receptor radionuclide therapy (PRRT) helps to optimize the injected activity, to prevent kidney or red marrow toxicity, while giving the highest absorbed dose to tumors. The aim of this study was to evaluate whether direct 90 Y bismuth germanate or lutetium yttrium orthosilicate time-of-flight PET was accurate enough to provide dosimetry estimates suitable to 90 Y PRRT. Method: To overcome the statistical uncertainty arising from the low 90 Y positron counting rate, the computation of the cortex mean-absorbed dose was divided into 4 steps: delineation of the cortex volume of interest (VOI) on the CT scan, determination of the recovery coefficient from the cortex VOI using the point-spread function of the whole imaging process, determination of the mean cortex-absorbed dose per unit cumulated activity in the cortex (S cortex)cortex value) from the cortex VOI using a 90 Y voxel S value kernel, and determination of the number of decays in the cortex VOI from the PET reconstruction. Our 4-step method was evaluated using an anthropomorphic abdominal phantom containing a fillable kidney phantom based on the MIRD kidney model. Vertebrae with an attenuation similar to that of bone were also modeled. Two tumors were modeled by 7-mL hollow acrylic spheres and the spleen by a plastic bag. Activities corresponded to typical tissue uptake in a first 90 Y-DOTATOC cycle of 4.4 GBq, considered as free of significant renal toxicity. Eight successive 45-min scans were acquired on both systems. Results: Both PET systems were successful in determining absorbed dose to modeled tumors but failed to provide accurate red marrow dosimetry. Renal cortex dosimetry was reproducible for both PET systems, with an accuracy of 3% for the bismuth germanate system but only 18% for the lutetium yttrium orthosilicate time-of-flight system, which was hindered by the natural radioactivity of the crystal, especially in the most attenuated area of the kidney. Conclusion: This study supports the use of direct 90 Y PET of the first PRRT cycle to assess the kidney-absorbed dose and optimize the injected activity of the following cycles.
Journal of Nuclear Medicine, 2009
Dosimetric calculations are performed with an increasing frequency before or after treatment in targeted radionuclide therapy, as well as for radiation protection purposes in diagnostic nuclear medicine. According to the MIRD committee formalism, the mean absorbed dose to a target is given by the product of the cumulated activity and a dose-conversion factor, known as the S factor. Standard S factors have been published for mathematic phantoms and for unit-density spheres. The accuracy of the results from the use of these S factors is questionable, because patient morphology can vary significantly. The aim of this work was to investigate differences between patient-specific dosimetric results obtained using Monte Carlo methodology and results obtained using S factors calculated on standard models. Methods: The CT images of 9 patients, who ranged in size, were used. Patient-specific S factors for 131 I were calculated with the MCNPX2.5.0 Monte Carlo code using a tool for personalized internal dose assessment, OEDIPE; standard S factors from OLINDA/EXM were compared against the patient-specific S factors. Furthermore, realistic biodistributions and cumulated activities for normal organs and tumors were used, and mean organ-and tumor-absorbed doses calculated with OEDIPE and OLINDA/EXM were compared. Results: The ratio of the standard and the patient-specific S factors were between 0.49 and 1.84 for a target distant from the source for 4 organs and 2 tumors studied as source and targets. For the case of self-irradiation, the equivalent ratio ranged between 0.45 and 2.47 and between 1.00 and 1.06 when mass correction was applied. Differences in mean absorbed doses were as high as 140% when realistic cumulated activity values were used. These values decreased to less than 26% in all cases studied when mass correction was applied to the self-irradiation given by OLINDA/EXM. Conclusion: Standard S factors can yield mean absorbed doses for normal organs or tumors with a reasonable accuracy (26% for the cases studied) as compared with absorbed doses calculated with Monte Carlo, provided that they have been corrected for mass.
Voxeldose: A Computer Program for 3-D Dose Calculation in Therapeutic Nuclear Medicine
Cancer Biotherapy and Radiopharmaceuticals, 2003
A computer program, VoxelDose, was developed to calculate patient specific 3-D-dose maps at the voxel level. The 3-D dose map is derived in three steps: i) The SPECT acquisitions are reconstructed using a filtered back projection method, with correction for attenuation and scatter; ii) the 3-D cumulated activity map is generated by integrating the SPECT data; and iii) a 3-D dose map is computed by convolution (using the Fourier Transform) of the cumulated activity map and corresponding MIRD voxel S values. To validate the VoxelDose software, a Liqui-Phil™ abdominal phantom with four simulated organ inserts and one spherical tumor (radius 4.2 cm) was filled with known activity concentrations of 111 In. Four cylindrical calibration tubes (from 3.7 to 102 kBq/mL) were placed on the phantom. Thermoluminescent mini-dosimeters (mini-TLDs) were positioned on the surface of the organ inserts. Percent differences between the known and measured activity concentrations were determined to be 12.1 (tumor), 1.8 (spleen), 1.4, 8.1 (right and left kidneys), and 38.2% (liver), leading to percent differences between the calculated and TLD measured doses of 41, 16, 3, 5, and 62%. Large differences between the measured and calculated dose in the tumor and the liver may be attributed to several reasons, such as the difficulty in precisely associating the position of the TLD to a voxel and limits of the quantification method (mainly the scatter correction and partial volume effect). Further investigations should be performed to better understand the impact of each effect on the results and to improve absolute quantification. For all other organs, activity concentration measurements and dose calculations agree well with the known activity concentrations.