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Molecular radiotherapy is a rapidly developing field with new vector and isotope combinations continually added to market. As with any radiotherapy treatment, it is vital that the absorbed dose and toxicity profile are adequately characterised. Methodologies for absorbed dose calculations for radiopharmaceuticals were generally developed to characterise stochastic effects and not suited to calculations on a patient-specific basis. There has been substantial scientific and technological development within the field of molecular radiotherapy dosimetry to answer this challenge. The development of imaging systems and advanced processing techniques enable the acquisition of accurate measurements of radioactivity within the body. Activity assessment combined with dosimetric models and radiation transport algorithms make individualised absorbed dose calculations not only feasible, but commonplace in a variety of commercially available software packages. The development of dosimetric parameters beyond the absorbed dose has also allowed the possibility to characterise the effect of irradiation by including biological parameters that account for radiation absorbed dose rates, gradients and spatial and temporal energy distribution heterogeneities. Molecular radiotherapy is in an exciting time of its development and the application of dosimetry in this field can only have a positive influence on its continued progression. • Molecular radiotherapy is a rapidly developing field. • There have been significant advances in quantitative imaging and dosimetry for molecular radiotherapy. • Dosimetry is now feasible in the clinical environment. • Dosimetry will enable the continued success and development of molecular radiotherapy. [ABSTRACT FROM AUTHOR]

The authors discuss a modern curriculum developed by the European Federation of Organisations for Medical Physics (EFOMP) and the European Association of Nuclear Medicine (EANM) specifically for the education and training of medical physicists in nuclear medicine. The topics covered by the main sections of the curriculum include the fundamental physics knowledge and measurement skills expected of all physicists. Other areas addressed by the curricula include professionalism and communication.

A kinetic model analysis has been proposed to assess absorbed dose to an arbitrary tissue in [¹⁸F]-fluorodeoxyglucose ([¹⁸F]-FDG) positron emission tomography (PET) imaging, whose efficiency is demonstrated in physiological brain, by comparing calculated estimates with human literature data. First, an analytic solution for the tissue [¹⁸F]-FDG time-activity curve has been derived from kinetic model analysis, assuming reversible radiotracer trapping. Then, integrating this solution from the time of tracer administration to infinity yielded analytic solutions for cumulated activity (and hence for the ratio of cumulated/injected activity) and the percentage of tracer uptake for an arbitrary tissue. Calculated estimates from these analytic solutions for the whole gray and white matter have been found in very good agreement with human literature data: 7.55 versus 6.57 (±1.51) MBq·hour (per unit of administered activity of 37 MBq), 0.204 versus 0.220 (±0.090) hour, and 6.25% versus 6.90%, respectively. This study concludes that the proposed kinetic model analysis has proven effective in assessing absorbed dose to human brain in [¹⁸F]-FDG PET imaging, under physiological conditions. This study suggests that this model could be further developed to assess absorbed dose to other tissues, either healthy or pathological, and also it could be further considered by involving other PET tracer features. [ABSTRACT FROM AUTHOR]

The article comments on the use of therapeutic radiopharmaceuticals or radiotherapy for the treatment of various diseases including cancer and tumors. It focuses on the achievements of the Dosimetry Task Group, a committee of the European Association of Nuclear Medicine (EANM), founded in 2001. The effectiveness of radiotherapy, and methods of dosimetry are discussed. Benefits of molecular radiotherapy (MRT) in comparison to chemotherapy, and MRT cost-related issues are also discussed.

The assessment and management of risks associated with exposures to ionising radiation are defined by the general radiological protection system, proposed by the International Commission on Radiological Protection (ICRP). This system is regarded by a large majority of users as a robust system although there are a number of dissenting voices, claiming that it is not suitable for estimating the risks resulting from internal exposures. One of the specific issues of internal exposure involves short-range radiations such as Auger and beta particles. Auger- and beta-emitting radionuclides can be distributed preferentially in certain tissue structures and even in certain cellular organelles, according to their chemical nature and the vector with which they are associated. Given the limited range of the low-energy electrons in biological matter, this heterogeneous distribution can generate highly localised energy depositions and exacerbate radiotoxic responses at cellular level. These particularities in energy distribution and cellular responses are not taken into account by the conventional methods for the assessment of risk. Alternative systems have been proposed, based on dosimetry conducted at the cellular or even molecular level, whose purpose is to determine the energy deposition occurring within the DNA molecule. However, calculation of absorbed doses at the molecular level is not sufficient to ensure a better assessment of the risks incurred. Favouring such a microdosimetric approach for the risk assessments would require a comprehensive knowledge of the biological targets of radiation, the dose-response relationships at the various levels of organisation, and the mechanisms leading from cellular energy deposition to the appearance of a health detriment. The required knowledge is not fully available today and it is not yet possible to link an intracellular energy deposition to a probability of occurrence of health effects or to use methods based on cellular dosimetry directly. The imperfections of the alternative approaches proposed so far should not discourage efforts. Protection against exposure to Auger and low-energy beta emitters would benefit from mechanistic studies, dedicated to the study of energy depositions of the radionuclides in various cellular structures, but also from radiotoxicological studies to define the relative biological effectiveness of the various Auger emitters used in medicine and of certain low-energy beta emitters, whose behaviour may depend greatly on their chemical form during intake. The scientific expertise, as well as the human and physical resources needed to conduct these studies, is available. They could be now mobilised into international low-dose research programmes, in order to ultimately improve the protection of people exposed to these specific radionuclides. [ABSTRACT FROM AUTHOR]

Abstract: We report on a new nuclear medical imaging technique based on the measurement of the emitter location in the three dimensions with a few mm spatial resolution using β+γ emitters. Such measurement could be realized thanks to a new kind of radio-nuclides which emit a γ-ray quasi-simultaneously with the β+ decay. The most interesting radio-nuclide candidate, namely 44Sc, will be potentially produced at the Nantes cyclotron ARRONAX. The principle is to reconstruct the intersection of the classical line of response (obtained with a standard PET camera) with the direction cone defined by the third γ-ray. The emission angle measurement of this additional γ-ray involves the use of a Compton telescope for which a new generation of camera based on a liquid xenon (LXe) time projection chamber is considered. GEANT3 simulations of a large acceptance LXe Compton telescope combined with a commercial micro-PET (LSO crystals) have been performed and the obtained results will be presented. They demonstrate that a good image can be obtained from the accumulation of each three-dimensional measured position. A spatial resolution of 2.3mm has been reached with an injected activity of 0.5MBq for a 44Sc point source emitter. [Copyright &y& Elsevier]

Background: The aim of this study was to compare a commercial dosimetry workstation (PLANET® Dose) and the dosimetry approach (GE Dosimetry Toolkit® and OLINDA/EXM® V1.0) currently used in our department for quantification of the absorbed dose (AD) to organs at risk after peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE. Methods: An evaluation on phantom was performed to determine the SPECT calibration factor variations over time and to compare the Time Integrated Activity Coefficients (TIACs) obtained with the two approaches. Then, dosimetry was carried out with the two tools in 21 patients with neuroendocrine tumours after the first and second injection of 7.2 ± 0.2 GBq of [177Lu]Lu-DOTA-TATE (40 dosimetry analyses with each software). SPECT/CT images were acquired at 4 h, 24 h, 72 h and 192 h post-injection and were reconstructed using the Xeleris software (General Electric). The liver, spleen and kidneys masses and TIACs were determined using Dosimetry Toolkit® (DTK) and PLANET® Dose. The ADs were calculated using OLINDA/EXM® V1.0 and the Local Deposition Method (LDM) or Dose voxel-Kernel convolution (DK) on PLANET® Dose. Results: With the phantom, the 3D calibration factors showed a slight variation (0.8% and 3.3%) over time, and TIACs of 225.19 h and 217.52 h were obtained with DTK and PLANET® Dose, respectively. In patients, the root mean square deviation value was 8.9% for the organ masses, 8.1% for the TIACs, and 9.1% and 7.8% for the ADs calculated with LDM and DK, respectively. The Lin's concordance correlation coefficient was 0.99 and the Bland–Altman plot analysis estimated that the AD value difference between methods ranged from − 0.75 to 0.49 Gy, from − 0.20 to 0.64 Gy, and from − 0.43 to 1.03 Gy for 95% of the 40 liver, kidneys and spleen dosimetry analyses. The dosimetry method had a minor influence on AD differences compared with the image registration and organ segmentation steps. Conclusions: The ADs to organs at risk obtained with the new workstation PLANET® Dose are concordant with those calculated with the currently used software and in agreement with the literature. These results validate the use of PLANET® Dose in clinical routine for patient dosimetry after targeted radiotherapy with [177Lu]Lu-DOTA-TATE. [ABSTRACT FROM AUTHOR]

The article reflects on the conflict between treatment optimization and registration of radiopharmaceuticals with fixed activity posology in oncological nuclear medicine therapy. Topics include maximum tolerable absorbed dose approach in nuclear medicine therapy; posology in current radiopharmaceutical registrations; and optimization principle in radioembolization procedures.

In cellular dosimetry, common assumptions consider concentric spheres for nucleus and cell and uniform radionuclides distribution. These approximations do not reflect reality, specially in the situation of radioimmunotherapy with Auger emitters, where very short-ranged electrons induce hyper localised energy deposition. A realistic cellular dosimetric model was generated to give account of the real geometry and activity distribution, for non-internalizing and internalizing antibodies (mAbs) labelled with Auger emitter I-125. The impact of geometry was studied by comparing the real geometry obtained from confocal microscopy for both cell and nucleus with volume equivalent concentric spheres. Non-uniform and uniform source distributions were considered for each mAbs distribution. Comparisons in terms of mean deposited energy per decay, energy deposition spectra and energy-volume histograms were calculated using Geant4. We conclude that realistic models are needed, especially when energy deposition is highly non-homogeneous due to source distribution. [ABSTRACT FROM AUTHOR]

Purpose: The dosimetric assessment of novel radiotracers represents a legal requirement in most countries. While the techniques for the computation of internal absorbed dose in a therapeutic context have made huge progresses in recent years, in a diagnostic scenario the absorbed dose is usually extracted from model-based lookup tables, most often derived from International Commission on Radiological Protection (ICRP) or Medical Internal Radiation Dose (MIRD) Committee models. The level of approximation introduced by these models may impact the resulting dosimetry. The aim of this work is to establish whether a more refined approach to dosimetry can be implemented in nuclear medicine diagnostics, by analyzing a specific case. Methods: The authors calculated absorbed doses to various organs in six healthy volunteers administered with flutemetamol (18F) injection. Each patient underwent from 8 to 10 whole body 3D PET/CT scans. This dataset was analyzed using a Monte Carlo (MC) application developed in-house using the toolkit GATE that is capable to take into account patient-specific anatomy and radiotracer distribution at the voxel level. They compared the absorbed doses obtained with GATE to those calculated with two commercially available software: OLINDA/EXM and STRATOS implementing a dose voxel kernel convolution approach. Results: Absorbed doses calculated with GATE were higher than those calculated with OLINDA. The average ratio between GATE absorbed doses and OLINDA'S was 1.38 ± 0.34 a (from 0.93 to 2.23). The discrepancy was particularly high for the thyroid, with an average GATE/OLINDA ratio of 1.97 ± 0.83 a for the six patients. Differences between STRATOS and GATE were found to be higher. The average ratio between GATE and STRATOS absorbed doses was 2.51 ± 1.21 a (from 1.09 to 6.06). Conclusions: This study demonstrates how the choice of the absorbed dose calculation algorithm may introduce a bias when gamma radiations are of importance, as is the case in nuclear medicine diagnostics. [ABSTRACT FROM AUTHOR]

Abstract: An accurate modeling of radial energy deposition around ion tracks is a key requirement of radiation transport software used for simulations in radiobiology at the sub-cellular scale. The work presented in this paper is part of the on-going benchmarking of the “Geant4-DNA” physics processes and models, which are available in the Geant4 Monte Carlo simulation toolkit for the low energy transport of particles in liquid water. We present for the first time radial dose distributions of incident ion tracks simulated with “Geant4-DNA”. Simulation results are compared to other results available in the literature, obtained from analytical calculations, step-by-step Monte Carlo simulations and measurements. They show a reasonable agreement with reference data. [Copyright &y& Elsevier]

Purpose: Dynamic microPET imaging has advantages over traditional organ harvesting, but is prone to quantification errors in small volumes. Hybrid imaging, where microPET activities are cross-calibrated using post scan harvested organs, can improve quantification. Organ harvesting, dynamic imaging and hybrid imaging were applied to determine the human and mouse radiation dosimetry of 6-[18 F]fluoro-L-DOPA and 2-[18 F]fluoro-L-tyrosine and compared.Procedures: Two-hour dynamic microPET imaging was performed with both tracers in four separate mice for 18 F-FDOPA and three mice for 18 F-FTYR. Organ harvesting was performed at 2, 5, 10, 30, 60 and 120 min post tracer injection with n = 5 at each time point for 18 F-FDOPA and n = 3 at each time point for 18 F-FTYR. Human radiation dosimetry projected from animal data was calculated for the three different approaches for each tracer using OLINDA/EXM. S-factors for the MOBY phantom were used to calculate the animal dosimetry.Results: Correlations between dose estimates based on organ harvesting and imaging was improved from r = 0.997 to r = 0.999 for 18 F-FDOPA and from r = 0.985 to r = 0.996 (p < 0.0001 for all) for 18 F-FTYR by using hybrid imaging.Conclusion: Hybrid imaging yields comparable results to traditional organ harvesting while partially overcoming the limitations of pure imaging. It is an advantageous technique in terms of number of animals needed and labour involved. [ABSTRACT FROM AUTHOR]

Purpose: Dynamic microPET imaging has advantages over traditional organ harvesting, but is prone to quantification errors in small volumes. Hybrid imaging, where microPET activities are cross-calibrated using post scan harvested organs, can improve quantification. Organ harvesting, dynamic imaging and hybrid imaging were applied to determine the human and mouse radiation dosimetry of 6-[18 F]fluoro- l-DOPA and 2-[18 F]fluoro- l-tyrosine and compared. Procedures: Two-hour dynamic microPET imaging was performed with both tracers in four separate mice for 18 F-FDOPA and three mice for 18 F-FTYR. Organ harvesting was performed at 2, 5, 10, 30, 60 and 120 min post tracer injection with n = 5 at each time point for 18 F-FDOPA and n = 3 at each time point for 18 F-FTYR. Human radiation dosimetry projected from animal data was calculated for the three different approaches for each tracer using OLINDA/EXM. S-factors for the MOBY phantom were used to calculate the animal dosimetry. Results: Correlations between dose estimates based on organ harvesting and imaging was improved from r = 0.997 to r = 0.999 for 18 F-FDOPA and from r = 0.985 to r = 0.996 ( p < 0.0001 for all) for 18 F-FTYR by using hybrid imaging. Conclusion: Hybrid imaging yields comparable results to traditional organ harvesting while partially overcoming the limitations of pure imaging. It is an advantageous technique in terms of number of animals needed and labour involved. [ABSTRACT FROM AUTHOR]

Modeling the radio-induced effects in biological medium still requires accurate physics models to describe the interactions induced by all the charged particles present in the irradiated medium in detail. These interactions include inelastic as well as elastic processes. To check the accuracy of the very low energy models recently implemented into the GEANT4 toolkit for modeling the electron slowing-down in liquid water, the simulation of electron dose point kernels remains the preferential test. In this context, we here report normalized radial dose profiles, for mono-energetic point sources, computed in liquid water by using the very low energy “GEANT4-DNA” physics processes available in the GEANT4 toolkit. In the present study, we report an extensive intra-comparison of profiles obtained by a large selection of existing and well-documented Monte-Carlo codes, namely, EGSnrc, PENELOPE, CPA100, FLUKA and MCNPX. [ABSTRACT FROM AUTHOR]

Abstract: Monte Carlo simulations of S-values have been carried out with the Geant4-DNA extension of the Geant4 toolkit. The S-values have been simulated for monoenergetic electrons with energies ranging from 0.1keV up to 20keV, in liquid water spheres (for four radii, chosen between 10nm and 1μm), and for electrons emitted by five isotopes of iodine (131, 132, 133, 134 and 135), in liquid water spheres of varying radius (from 15μm up to 250μm). The results have been compared to those obtained from other Monte Carlo codes and from other published data. The use of the Kolmogorov–Smirnov test has allowed confirming the statistical compatibility of all simulation results. [Copyright &y& Elsevier]

Many recent publications in nuclear medicine contain data on dosimetric findings for existing and new diagnostic and therapeutic agents. In many of these articles, however, a description of the methodology applied for dosimetry is lacking or important details are omitted. The intention of the EANM Dosimetry Committee is to guide the reader through a series of suggestions for reporting dosimetric approaches. The authors are aware of the large amount of data required to report the way a given clinical dosimetry procedure was implemented. Another aim of this guidance document is to provide comprehensive information for preparing and submitting publications and reports containing data on internal dosimetry. This guidance document also contains a checklist which could be useful for reviewers of manuscripts submitted to scientific journals or for grant applications. In addition, this document could be used to decide which data are useful for a documentation of dosimetry results in individual patient records. This may be of importance when the approval of a new radiopharmaceutical by official bodies such as EMA or FDA is envisaged. [ABSTRACT FROM AUTHOR]

Point kernels describe the energy deposited at a certain distance from an isotropic point source and are useful for nuclear medicine dosimetry. They can be used for absorbed-dose calculations for sources of various shapes and are also a useful tool when comparing different Monte Carlo (MC) codes. The aim of this study was to compare point kernels calculated by using the mixed MC code, PENELOPE (v. 2006), with point kernels calculated by using the condensed-history MC codes, ETRAN, GEANT4 (v. 8.2), and MCNPX (v. 2.5.0). Point kernels for electrons with initial energies of 10, 100, 500, and 1 MeV were simulated with PENELOPE. Spherical shells were placed around an isotropic point source at distances from 0 to 1.2 times the continuous-slowing-down-approximation range (R(CSDA)). Detailed (event-by-event) simulations were performed for electrons with initial energies of less than 1 MeV. For 1-MeV electrons, multiple scattering was included for energy losses less than 10 keV. Energy losses greater than 10 keV were simulated in a detailed way. The point kernels generated were used to calculate cellular S-values for monoenergetic electron sources. The point kernels obtained by using PENELOPE and ETRAN were also used to calculate cellular S-values for the high-energy beta-emitter, 90Y, the medium-energy beta-emitter, 177Lu, and the low-energy electron emitter, 103mRh. These S-values were also compared with the Medical Internal Radiation Dose (MIRD) cellular S-values. The greatest differences between the point kernels (mean difference calculated for distances, <0.9 r/R(CSDA)), using PENELOPE and those from ETRAN, GEANT4, and MCNPX, were 3.6%, 6.2%, and 14%, respectively. The greatest difference between the cellular S-values for monoenergetic electrons was 1.4%, 2.5%, and 6.9% for ETRAN, GEANT4, and MCNPX, respectively, compared to PENELOPE, if omitting the S-values when the activity was distributed on the cell surface for 10-keV electrons. The largest difference between the cellular S-values for the radionuclides, between PENELOPE and ETRAN, was seen for 177Lu (1.2%). There were large differences between the MIRD cellular S-values and those obtained from PENELOPE: up to 420% for monoenergetic electrons and <22% for the radionuclides, with the largest difference for 103mRh. In conclusion, differences were found between the point kernels generated by different MC codes, but these differences decreased when cellular S-values were calculated, and decreased even further when the energy spectra of the radionuclides were taken into consideration. [ABSTRACT FROM AUTHOR]