BACKGROUND:The progression of targeted radionuclide therapy requires the development of dosimetry software accounting for patient-specific biokinetics. New functionalities were thus developed in the OEDIPE software, to deal with multiple 3D images or multiple planar images and a SPECT image.MATERIEL & METHOD:Methods were implemented to recover patient biokinetics in volumes of interest. If several 3D SPECT images are available, they are registered to a reference CT scan. When several planar images and a single SPECT are available, the planar images are registered to the SPECT and counts of the planar images converted to activity. To validate these developments, six SPECT/CT and planar images of a Jaszczak phantom containing I-131 were acquired at different dates. Cumulated activity was estimated in each sphere using the SPECT/CT images only or the planar series associated to one SPECT/CT. Biokinetics and doses in lesions and in the lungs of a patient treated with I-131 for differentiated thyroid cancer were then estimated using four planar images and a SPECT/CT scan. Whole-body retention data were used to compare the biokinetics obtained from the planar and SPECT data.RESULTS:Activities and cumulated activities estimated using OEDIPE in the phantom spheres agreed well with the reference values for both approaches. Results obtained for the patient compared well with those derived from whole-body retention data.CONCLUSION:The implemented features allow automatic evaluation of patient-specific biokinetics from different series of patient images, enabling patient-specific dosimetry without the need for external software to estimate the cumulated activities in different VOIs.

To further improve the understanding of in vitro biological effects of incorporated radionuclides, it is essential to accurately determine cellular absorbed doses. In the case of β emitters, the cross-dose is a major contribution, and can involve up to millions of cells. Realistic and efficient computational models are needed for that purpose. Conventionally, distances between each cell are calculated and the related dose contributions are cumulated to get the total cross-dose (standard method). In this work, we developed a novel approach for the calculation of the cross-absorbed dose, based on the use of the radial distribution function (rdf)) that describes the spatial properties of the cellular model considered. The dynamic molecular tool LAMMPS was used to create 3D cellular models and compute rdfs for various conditions of cell density, volume size, and configuration type (lattice and randomized geometry). The novel method is suitable for any radionuclide of nuclear medicine. Here, the model was applied for the labeling of cells with 18F-FDG used for PET imaging, and first validated by comparison with other reference methods. Mean S cross values calculated with the novel approach versus the standard method agreed very well (relative differences less that 0.1%). Implementation of the rdf -based approach with LAMMPS allowed to achieved results considerably faster than with the standard method, the computing time decreasing from hours to seconds for 106 cells. The rdf -based approach was also faster and easier to accommodate more complex cellular models than the standard and other published methods. Finally, a comparative study of the mean S cross for different types of configuration was carried out, as a function of the cell density and the volume size, allowing to better understand the impact of the configuration on the cross-absorbed dose.

H Miloudi, M Locatelli, G Autret, D Balvay, A Desbrée, E Blanchardon, J M Bertho: application of RODES software to experimental biokinetic data for dose assessment in mice and rats. In support of experimental studies of chronic, long-term contamination in rodents, voxel-based computer models were built representing adult mice and juvenile, adult and elderly rats of both sexes. RODES software was created to calculate absorbed radiation doses to organs with these specific anatomical models. Absorbed doses were then calculated starting from previously published biokinetic data. Whole body doses showed less than 5% differences between calculation with RODES and calculation with the ICRP Publication 108 model for long term exposure to 90Sr of mice. Similar results were obtained for long term exposure to 137Cs. Dose distribution for 90Sr internal contamination also showed that the dose to the skeleton is six fold more as compared to the whole body dose while radiation dose to other organs is less than the mean whole body dose. These results underline the importance of using specific anatomical models according to the age and the sex of experimental animals.

PURPOSE:In Selective Internal Radiation Therapy (SIRT), 99mTc-MAA SPECT images are commonly used to predict microspheres distribution but recent works used 90Y-microspheres PET images. Nevertheless, evaluation of the predictive power of 99mTc-MAA has been hampered by the lack of reliable comparisons between 99mTc-SPECT and 90Y-PET images. Our aim was to determine the "in situ" optimisation procedure in order to reliably compare 99mTc-SPECT and 90Y-PET images and achieve optimal personal dosimetry. METHODS:We acquired 99mTc-SPECT/CT and 90Y-PET/CT images of NEMA and Jaszczak phantoms. We found the best reconstruction parameters for quantification and for volume estimations. We determined adaptive threshold curves on the volumetric reconstruction. We copied the optimised volumes on the quantitative reconstruction, named here the "cross volumes" technique. Finally, we compared 99mTc-SPECT and 90Y-PET Dose Volume Histograms. RESULTS:Our "in situ" optimisation procedure decreased errors on volumes and quantification (from -44.2% and -15.8% to -3.4% and -3.28%, respectively, for the 26.5mL PET phantom sphere). Moreover, 99mTc-SPECT and 90Y-PET DVHs were equivalent only after the optimisation procedure (difference in mean dose <5% for the three biggest spheres). CONCLUSIONS:This work showed that a preliminary "in situ" phantom study was necessary to optimise volumes and quantification of 99mTc-SPECT and 90Y-PET images and allowed to achieve a reliable comparison between patient treatment planning and post implant dosimetry, notably by the use of the "cross volumes" technique. Methodology developed in this work will enable robust evaluations of the predictive power of 99mTc-SPECT, as well as dose-response relationship and side effects in SIRT treatments.

1019 Objectives 223Ra-dichloride is the first alpha-emitter radiopharmaceutical that has received approval by the US Food and Drug Administration and marketing authorization from European Commission and for the treatment of patients with castration-resistant prostate cancer metastasized to bones. This radiopharmaceutical mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover such as bone metastases. To better determine the dose-limiting toxicities to bone marrow due to this new therapy and correlate absorbed dose to therapeutic response, patient-specific dosimetric studies are required. To that aim, it is necessary to compare 223Ra-dichloride uptake to bone lesion locations and its quantitative biodistribution into the bone by 223Ra emission images. Despite a low photon yield, planar imaging of 223Ra-dichloride was shown to be feasible on phantoms and patients allowing determination of biodistribution and pharmacokinetics. But no study has so far explored the feasibility of SPECT images and their optimization in clinics. Methods The experiments were conducted at the Hopital Europeen Georges Pompidou, in Paris (France), with an Infinia Hawkeye 4 gamma camera, equipped with a medium-energy collimator. The gamma camera imaging parameters were determined by measuring sensibility, spatial resolution and energy spectrum, with a syringe containing 350 kBq of 223Ra. A NEMA Body Phantom and a TORSO Phantom were used to evaluate the possibility of SPECT imaging and to determine the best reconstruction parameters available on clinical software. Results Images were acquired using three energy windows: 85 keV ± 20%, 154 keV ± 20% and 270 keV ± 10%. Camera sensitivity measured from the phantom study was 42.9, 12.7, and 12.6 cps/MBq for the 85, 154, and 270 keV windows, respectively. The spatial resolution (full-width at half-maximum) was respectively 1.4, 1.7 and 1.5 cm for the three energy windows. The visual quality of the SPECT (60 projections, 360° rotation, and 30s per view) images allows a clinical use. The best reconstruction parameters were determined. Conclusions This study has demonstrated that it was possible to obtain clinically relevant information from SPECT acquisitions of 223Ra. These results show the added value to acquire 3D images of patients to more precisely localize 223Ra biodistribution and estimate absorbed doses that will permit to establish the proper correlation with tumor response.

The Auger-electrons emitted by (99m)Tc have been recently associated with the induction of thyroid stunning in in vivo experiments in mice, making the dosimetry at the sub-cellular level of (99m)Tc a pertinent and pressing subject. The S-values for (99m)Tc were calculated using MCNP6, which was first validated for studies at the sub-cellular scale and for low energies electrons. The calculation was then performed for (99m)Tc within different cellular compartments in a single mouse thyroid follicle model, considering the radiative and non-radiative transitions of the (99m)Tc radiation spectrum. It was shown that the contribution of the (99m)Tc Auger and low energy electrons to the absorbed dose to the follicular cells' nucleus is important, being at least of the same order of magnitude compared to the emitted photons' contribution and cannot be neglected. The results suggest that Auger-electrons emitted by (99m)Tc play a significant role in the occurrence of the thyroid stunning effect in mice.

Superparamagnetic iron oxide (SPIO) nanoparticles are widely used as contrast agents for nuclear magnetic resonance imaging (MRI), and can be modified for improved imaging or to become tissue-specific or even protein-specific. The knowledge of their detailed elemental composition characterisation and potential use in nuclear medicine applications, is, therefore, an important issue. X-ray fluorescence techniques such as particle induced X-ray emission (PIXE) or X-ray fluorescence spectrometry (XRF), can be used for elemental characterisation even in problematic situations where very little sample volume is available. Still, the fluorescence coefficient of Fe is such that, during the decay of the inner-shell ionised atomic structure, keV Auger electrons are produced in excess to X-rays. Since cross-sections for ionisation induced by keV electrons, for low atomic number atoms, are of the order of 103 barn, care should be taken to account for possible fluorescence effects caused by Auger electrons, which may lead to the wrong quantification of elements having atomic number lower than the atomic number of Fe. Furthermore, the same electron processes will occur in iron oxide nanoparticles containing 57Co, which may be used for nuclear medicine therapy purposes. In the present work, simple approximation algorithms are proposed for the quantitative description of radiative and non-radiative processes associated with Auger electrons cascades. The effects on analytical processes and nuclear medicine applications are quantified for the case of iron oxide nanoparticles, by calculating both electron fluorescence emissions and energy deposition on cell tissues where the nanoparticles may be embedded.

A patient treated with 3.7 GBq of I-131 after thyroidectomy for a papillary carcinoma presented, three days after iodine administration, an unusually elevated dose rate at 1 m. Scintigraphy and Single Photon Emission Computed Tomography coupled with Computed Tomography (SPECT/CT) were performed and showed a significant iodine uptake at the anterior mediastinal level due to the presence of a residual intrathoracic goitre. The proximity between this iodofixant goitre and the surrounding tissues prompted dose estimations to local organs at risk, in particular the heart. Dosimetric estimations were initially performed with OLINDA/EXM software, commonly used in nuclear medicine. More personalised doses were then calculated using the OEDIPE software associated with the Monte Carlo code MCNPX. Calculations with the OLINDA/EXM software enabled a first assessment of the mean absorbed dose to the heart, estimated at about 2 Gy for an uptake of 56% of the administered activity. In a second step, the use of the OEDIPE software allowed us to take into account the specific geometry of the patient as well as the distribution of iodine uptake at a mediastinal level and to determine a mean absorbed dose of approximately 1 Gy to the heart. Thus, the use of a voxelised phantom based on CT images of the patient, associated with direct Monte Carlo calculations, enabled us to improve the calculation of the absorbed doses to the heart compared with the use of a standard anthropomorphic phantom.

Purpose: To perform a dosimetry study at the sub-cellular scale of Auger-electron emitter 99m-Tc using a mouse single thyroid cellular model to investigate the contribution of the 99m-Tc Auger-electrons to the absorbed dose and possible link to the thyroid stunning in in vivo experiments in mice, recently reported in literature. Methods: The simulation of S-values for Auger-electron emitting radionuclides was performed using both the recent MCNP6 software and the Geant4-DNA extension of the Geant4 toolkit. The dosimetric calculations were validated through comparison with results from literature, using a simple model of a single cell consisting of two concentric spheres of unit density water and for six Auger-electron emitting radionuclides. Furthermore, the S-values were calculated using a single thyroid follicle model for uniformly distributed 123-I and 125-I radionuclides and compared with published S-values. After validation, the simulation of the S-values was performed for the 99m-Tc radionuclide within the several mouse thyroid follicle cellular compartments, considering the radiative and non-radiative transitions of the 99m-Tc radiation spectrum. Results: The calculated S-values using MCNP6 are in good agreement with the results from literature, validating its use for the 99m-Tc S-values calculations. The most significant absorbed dose corresponds to the case where the radionuclide is uniformly distributed in the follicular cell's nucleus, with a S-value of 7.8 mGy/disintegration, due mainly to the absorbed Auger-electrons. The results show that, at a sub-cellular scale, the emitted X-rays and gamma particles do not contribute significantly to the absorbed dose. Conclusion: In this work, MCNP6 was validated for dosimetric studies at the sub-cellular scale. It was shown that the contribution of the Auger-electrons to the absorbed dose is important at this scale compared to the emitted photons’ contribution and can't be neglected. The obtained S-values of Auger-electron emitting 99m-Tc radionuclide will be presented and discussed.

A recently published detailed and exhaustive paper on cross-sections for ionisation induced by keV electrons clearly shows that electron phenomena occurring in parallel with X-ray processes may have been dramatically overlooked for many years, mainly when low atomic number species are involved since, in these cases, the fluorescence coefficient is smaller than the Auger yield. An immediate problem is encountered while attempting to tackle the issue. Accounting for electron phenomena requires the knowledge of the stopping power of electrons within, at least, a reasonably small error. Still, the Bethe formula for stopping powers is known to not be valid for electron energies below 30 keV, and its use leads to values far off experimental ones. Recently, a few authors have addressed this problem and both detailed tables of electron stopping powers for various atomic species and attempts to simplify the calculations, have emerged. Nevertheless, its implementation in software routines to efficiently calculate keV electron effects in materials quickly becomes a bit cumbersome. Following a procedure already used to establish efficient methods to calculate ionisation cross-sections by protons and alpha particles, it became clear that a simple polynomial approximation could be set, which allows retrieving the electronic stopping powers with errors of less than 20% for energies above 500 eV and less than 50% for energies between 50 eV and 500 eV. In this work, we present this approximation which, based on just six parameters, allows to recover electron stopping power values that are less than 20% different from recently published experimentally validated tabulated data.

Purpose:With a growing demand of alpha‐emitting radiopharmaceuticals, especially Xofigo (223RaCl2) which is used in the treatment of metastatic bone disease, the optimization of dosimetry becomes necessary. Indeed, in Europe, as stated on the council directive 2013/59/euratom, exposures of target volumes for radiotherapeutic purposes shall be individually planned taking into account that doses to non‐target volumes and tissues shall be as low as reasonably achievable. To that aim, the possibility of imaging 223Ra was first investigated.Methods:The experiments were conducted at the Hopital Europeen Georges Pompidou with an Infinia Hawkeye 4 gamma camera, equipped with a medium‐energy collimator. Imaging parameters, such as sensibility, spatial resolution and energy spectrum, were determined using several physical phantoms with a source of 6 MBq of 223Ra. Bone metastases were modeled with a NEMA Body Phantom to investigate image degradation based on the concentration of 223Ra.Results:The acquired energy spectrum allowed to visualize several photon peaks: at 85, 154 and 270 keV. Camera sensitivity measured from the phantom study was 102.3 cps/MBq for the 85 keV ± 20 %, 89.9 cps/MBq for the 154 ± 20 % window and 65.4 cps/MBq for the 270 ± 10 % window. The spatial resolution (full‐width at half‐maximum) was respectively 1.7, 1.9 and 1.8 cm for the three energy windows. SPECT/CT images of NEMA Body Phantom without and with attenuation have permitted to determine the best reconstruction parameters.Conclusion:This study has demonstrated that it is possible to obtain clinically relevant information from images of 223Ra. All these results will be valuable to analyze biodistribution imaging of the radiopharmaceutical in the patient body and go further in the reconstruction of patient images in order to personalize the dosimetry.

Chez un patient ayant reçu 3,7 GBq d’131I après thyroïdectomie totale pour un carcinome papillaire, la mesure du débit de dose à 1 m, réalisée de façon systématique 3 jours après le traitement, a montré une valeur anormalement élevée. Une scintigraphie et une Tomographie d’Émission MonoPhotonique associée à une Tomodensitométrie (TEMP/TDM) ont alors été réalisées et ont montré une fixation importante de l’iode au niveau médiastinal antérieur due à la présence d’un goitre endothoracique résiduel. Compte tenu de la proximité entre ce goitre iodofixant et les tissus avoisinants, les doses reçues par les organes à risque les plus proches, notamment le cœur, ont été évaluées. Cette évaluation a été réalisée, dans un premier temps, avec le logiciel OLINDA/EXM, couramment utilisé en médecine nucléaire. Des doses plus personnalisées ont ensuite été calculées à l’aide du logiciel OEDIPE associé au code Monte Carlo MCNPX. Les calculs effectués avec le logiciel OLINDA/EXM ont permis d’évaluer la dose moyenne absorbée au cœur à environ 2 Gy avec une fixation de 56 % de l’activité administrée. Dans un second temps, l’utilisation du logiciel OEDIPE a permis de prendre en compte la géométrie spécifique du patient ainsi que la répartition de la fixation d’iode au niveau médiastinal et de déterminer une dose absorbée moyenne d’environ 1 Gy au cœur. Ainsi, l’utilisation d’un fantôme voxelisé, basé sur les images TDM du patient, associé à un calcul Monte Carlo direct a permis d’optimiser le calcul des doses absorbées au cœur par rapport à l’utilisation d’un fantôme anthropomorphe standard.