Henri Becquerel's discovery of radioactivity - 125 years later.

This year it is 125 years since Henri Becquerel accidentally discovered radioactivity. It has been argued that this was the result after Becquerel's long, systematic research into the phenomenon of luminescence. Becquerel's discovery, together with Marie and Pierre Curie's discovery of radium, became the breakthrough for the 20th century research in medical radiation physics and the use of radioactivity in medicine. In this paper, we draw attention to Becquerel's discovery and the impact it had on medicine and society.

Quantitative γ-H2AX immunofluorescence method for DNA double-strand break analysis in testis and liver after intravenous administration of 111InCl3.

BACKGROUND: It is well known that a severe cell injury after exposure to ionizing radiation is the induction of DNA double-strand breaks (DSBs). After exposure, an early response to DSBs is the phosphorylation of the histone H2AX molecule regions adjacent to the DSBs, referred to as γ-H2AX foci. The γ-H2AX assay after external exposure is a good tool for investigating the link between the absorbed dose and biological effect. However, less is known about DNA DSBs and γ-H2AX foci within the tissue microarchitecture after internal irradiation from radiopharmaceuticals. Therefore, in this study, we aimed to develop and validate a quantitative ex vivo model using γ-H2AX immunofluorescence staining and confocal laser scanning microscopy (CLSM) to investigate its applicability in nuclear medicine dosimetry research. Liver and testis were selected as the organs to study after intravenous administration of 111InCl3. RESULTS: In this study, we developed and validated a method that combines ex vivo γ-H2AX foci labeling of tissue sections with in vivo systemically irradiated mouse testis and liver tissues. The method includes CLSM imaging for intracellular cell-specific γ-H2AX foci detection and quantification and absorbed dose calculations. After exposure to ionizing radiation from 111InCl3, both hepatocytes and non-hepatocytes within the liver showed an absorbed dose-dependent elevation of γ-H2AX foci, whereas no such correlation was seen for the testis tissue. CONCLUSION: It is possible to detect and quantify the radiation-induced γ-H2AX foci within the tissues of organs at risk after internal irradiation. We conclude that our method developed is an appropriate tool to study dose-response relationships in animal organs and human tissue biopsies after internal exposure to radiation.

Testis dosimetry in individual patients by combining a small-scale dosimetry model and pharmacokinetic modeling-application of (111)In-Ibritumomab Tiuxetan (Zevalin(®)).

A heterogeneous distribution of radionuclides emitting low-energy electrons in the testicles may result in a significant difference between an absorbed dose to the radiosensitive spermatogonia and the mean absorbed dose to the whole testis. This study focused on absorbed dose distribution in patients at a finer scale than normally available in clinical dosimetry, which was accomplished by combining a small-scale dosimetry model with patient pharmacokinetic data. The activity in the testes was measured and blood sampling was performed for patients that underwent pre-therapy imaging with (111)In-Zevalin(®). Using compartment modeling, testicular activity was separated into two components: vascular and extravascular. The uncertainty of absorbed dose due to geometry variations between testicles was explored by an assumed activity micro-distribution and by varying the radius of the interstitial tubule. Results showed that the absorbed dose to germ cells might be strongly dependent on the location of the radioactive source, and may exceed the absorbed dose to the whole testis by as much as a factor of two. Small-scale dosimetry combined with compartmental analysis of clinical data proved useful for gauging tissue dosimetry and interpreting how intrinsic geometric variation influences the absorbed dose.

A small-scale anatomical dosimetry model of the liver.

Radionuclide therapy is a growing and promising approach for treating and prolonging the lives of patients with cancer. For therapies where high activities are administered, the liver can become a dose-limiting organ; often with a complex, non-uniform activity distribution and resulting non-uniform absorbed-dose distribution. This paper therefore presents a small-scale dosimetry model for various source-target combinations within the human liver microarchitecture. Using Monte Carlo simulations, Medical Internal Radiation Dose formalism-compatible specific absorbed fractions were calculated for monoenergetic electrons; photons; alpha particles; and (125)I, (90)Y, (211)At, (99m)Tc, (111)In, (177)Lu, (131)I and (18)F. S values and the ratio of local absorbed dose to the whole-organ average absorbed dose was calculated, enabling a transformation of dosimetry calculations from macro- to microstructure level. For heterogeneous activity distributions, for example uptake in Kupffer cells of radionuclides emitting low-energy electrons ((125)I) or high-LET alpha particles ((211)At) the target absorbed dose for the part of the space of Disse, closest to the source, was more than eight- and five-fold the average absorbed dose to the liver, respectively. With the increasing interest in radionuclide therapy of the liver, the presented model is an applicable tool for small-scale liver dosimetry in order to study detailed dose-effect relationships in the liver.

Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation.

75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups. The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.

Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with (177)Lu- and (90)Y-BR96 mAbs.

PURPOSE: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. METHODS: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with (90)Y- and (177)Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. RESULTS: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for (177)Lu and 12.5 Gy for (90)Y. CONCLUSIONS: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom weight, ranging from 225 g to 300 g, appeared to have no substantial effect for the estimated absorbed dose.

A small-scale anatomic model for testicular radiation dosimetry for radionuclides localized in the human testes.

UNLABELLED: The testis is a radiosensitive tissue. It contains a large number of lobules, which in turn are composed of convoluted seminiferous tubules. The epithelium inside each tubule consists of a complex mosaic of supporting cells and germ cells of different sizes and degrees of maturation. These cells are known to have diverse sensitivity to radiation, those with the highest sensitivity being the spermatogonia, which form part of the basal cell layer, and those with the lowest sensitivity being the mature sperm cells closest to the lumen of the tubule. For many years, the internal dosimetry community has discussed the need for improvements to bring about more detailed, cell-level testicular dosimetry. This paper presents a small-scale dosimetry model for calculation of S factors for several different source-target configurations within the testicular tissue. METHODS: A model of the testis was designed in which the lobules were approximated by a cross-section of seminiferous tubules arranged in a hexagonal pattern, with interstitial tissue between them. The seminiferous tubules were divided into concentric layers representing spermatogenic development in the seminiferous epithelium. S factors were calculated for electrons, photons, α-particles, and for (18)F, (90)Y, (99m)Tc, (111)In, (125)I, (131)I, (177)Lu, and (211)At using Monte Carlo simulations. RESULTS: For electrons with low energies the range was small, compared with the diameter of the seminiferous tubules, resulting in high energy deposition close to the source, whereas for higher electron energies more uniform energy deposition was seen, as expected. The same trend was seen for low-energy photons, whose mean free paths are small, compared with the diameter of the seminiferous tubules, resulting in high energy deposition close to the source, whereas for higher photon energies the location of the activity in the testis is less important. CONCLUSION: The model presented in this paper is a simplification of the organized chaos that constitutes the structure of the actual testis. However, it provides a relevant, small-scale anatomic model to help us understand the significance of the heterogeneity of radioactivity in this important radiosensitive tissue.

Monte Carlo calculations of absorbed doses in tumours using a modified MOBY mouse phantom for pre-clinical dosimetry studies.

BACKGROUND: Clinical treatment with radionuclides is usually preceded by biokinetic and dosimetry studies in small animals. Evaluation of the therapeutic efficacy 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 significance in the interpretation of radiobiological tumour response in pre-clinical studies.

Mouse S-factors based on Monte Carlo simulations in the anatomical realistic Moby phantom for internal dosimetry.

INTRODUCTION: Biokinetic and dosimetry studies in small animals often precede clinical radionuclide therapies. As in human studies, a reliable evaluation of therapeutic efficacy is essential and must be based on accurate dosimetry, which must be based on a realistic dosimetry model. The aim of this study was to evaluate the differences in the results when using a more anatomic realistic mouse phantom, as compared to previously mathematically described phantoms, based mainly on ellipsoids and cylinders. The difference in results from the two Monte Carlo codes, EGS4 and MCNPX 2.6a, was also evaluated. METHODS: An anatomical correct mouse phantom (Moby) was developed by Segars et al. for the evaluation and optimization of the in vivo imaging of mice. The Moby phantom is based on surfaces, which allows for an easy and flexible definition of organ sizes. It includes respiratory movements and a beating heart. It also allows for a redefinition of the location of several internal organs. The execution of the Moby program generates a three-dimensional voxel-based phantom of a specified size, which was modified and used as input for Monte Carlo simulations of absorbed fractions and S-factors. The radiation transport was simulated both with the EGS4 system and the MCNPX 2.6a code. Calculations were done for the radionuclides (18)F, (124)I, (131)I, (111)In, (177)Lu, and (90)Y. S-factors were calculated using in-house-developed IDL programs and compared with results from previously published models. RESULTS: The comparison of S-factors obtained by the Moby model and mathematical phantoms showed that these, in many cases, were within the same range, whereas for some organs, they were underestimated in the mathematical phantoms. The results were closer to the more anatomically realistic phantom than to the mathematical phantoms, with some exceptions. When investing differences between MCNPX 2.6a and EGS4 using the Moby phantom, results indicated some differences in absorbed fractions for electrons. This reason may be owing to differences in the codes regarding the theory for which electron transport are simulated. CONCLUSIONS: It is possible to calculate S-factors that are specific for small animals, such as mice. The Moby phantom is useful as a dosimetry model because it is anatomically realistic, but still very flexible, with 35 accurately segmented regions.

A case study of successful e-learning: a web-based distance course in medical physics held for school teachers of the upper secondary level.

Learning activities and course design in the new context of e-learning, such as in web-based courses involves a change both for teachers and students. The paper discusses factors important for e-learning to be successful. The development of an online course in medical physics and technology for high school teachers of physics, details of the course, and experience gained in connection with it are described. The course syllabus includes basics of radiation physics, imaging techniques using ionizing or non-ionizing radiation, and external and internal radiation therapy. The course has a highly didactic approach. The final task is for participants to design a course of their own centered on some topic of medical physics on the basis of the knowledge they have acquired. The aim of the course is to help the teachers integrate medical physics into their own teaching. This is seen as enhancing the interest of high school students in later studying physics, medical physics or some other branch of science at the university level, and as increasing the knowledge that they and people generally have of science. It is suggested that the basic approach taken can also have applicability to the training of medical, nursing or engineering students, and be used for continuing professional development in various areas.

Dosimetry calculations on a tissue level by using the MCNP4c2 Monte Carlo code.

OBJECTIVE: The aim of this study was to develop a MCNP4c2-code and to further refine the small-scale anatomy intestinal dosimetry model based on a EGS4-code developed by Jonsson et al.(1,2) METHOD: The small intestine was modeled as a hexagonal tube system and includes cross-dose contribution from activity in nearby intestine loops. The model includes villi (height, 500 microm), radiosensitive crypt cells (height, 150 microm), and an overlying mucus layer of thicknesses (5-200 microm). The developed intestinal model used in either of the two Monte Carlo codes make it possible to calculate S-values and subsequent mean absorbed dose to the radiation-sensitive crypt cells in the small intestinal wall by considering contributions from the self-dose and from the cross-dose from nearby intestinal loops. Results are given for monoenergetic electrons and photons and for full decay schemes of (99m)Tc, (111)In, (131)I, (67)Ga, (90)Y, and (211)At. RESULTS: Results show that the cross-dose from nearby intestinal loops is significant, and that the fraction of cumulated activity in the intestinal wall contents is important for accurate absorbed-dose estimation. CONCLUSION: It is evident from our study that previous Medical Internal Radiation Dose (MIRD) and International Conference on Radiological Protection (ICRP) models tend to overestimate the absorbed dose to the wall. Our work on the gastrointestinal tract model includes several noticeable refinements, as compared to the MIRD- and ICRP model, and the "onion shell" geometry can easily be transferred to similar geometrical dosimetry applications.

Crypt cell dosimetry for 99Tcm-sestamibi in a new small intestinal dosimetry model.

The aim of the study was to calculate the absorbed dose to the crypt cells in the small intestine from (99)Tc(m)-sestamibi excreted through the intestinal tract. The absorbed dose was calculated taking into consideration the biodistribution of the radiopharmaceutical in the small intestinal wall and its contents, based on data gathered in rats. Absorbed dose calculations were performed using a new intestinal model in which S values for crypt cells are given both for the intestinal wall and for the intestinal contents as source organs. A maximum of 6% of the injected activity was found to be located in the intestinal wall at 30 minutes after injection and 13% in the intestinal contents at 2 h, resulting in an absorbed dose of 8.9 microGy/MBq to the crypt cells. Assuming the activity to be located only in the wall, we calculate an absorbed dose to the crypt cells 2.5 times higher than if all the activity is assumed to be present in the intestinal contents. Using the new intestinal dosimetry model, together with detailed biokinetic data for the radiopharmaceutical from animal studies, it is possible to calculate the absorbed dose to the crypt cells, which is not possible when using external imaging.

A dosimetry model for the small intestine incorporating intestinal wall activity and cross-doses.

UNLABELLED: Current internal radiation dosimetry models for the small intestine, and for most walled organs, lack the ability to account for the activity uptake in the intestinal wall. In existing models the cross-dose from nearby loops of the small intestine is not taken into consideration. The aim of this investigation was to develop a general model for calculating the absorbed dose to the radiation-sensitive cells in the small intestinal mucosa from radionuclides located in the small intestinal wall or contents. METHODS: A model was developed for calculation of the self-dose and cross-dose from activity in the intestinal wall or contents. The small intestine was modeled as a cylinder with 2 different wall thicknesses and with an infinite length. Calculations were performed for various mucus thicknesses. S values were calculated using the EGS4 Monte Carlo simulation package with the PRESTA algorithm and the simulation results were integrated over the depth of the radiosensitive cells. The cross-organ dose was calculated by summing the dose contributions from other intestinal segments. Calculations of S values for self-dose and cross-dose were made for monoenergetic electrons, 0.050-10 MeV, and for the radionuclides (99m)Tc, (111)In, (131)I, (67)Ga, (90)Y, and (211)At. RESULTS: The self-dose S value from activity located in the small intestinal wall is considerably greater than the S values for self-dose from the contents and the cross-dose from wall and contents except for high electron energies. For all radionuclides investigated and for electrons 0.10-0.20 MeV and 8-10 MeV in energy, the cross-dose from activity in the contents is higher than the self-dose from the contents. The mucus thickness affects the S value when the activity is located in the contents. CONCLUSION: A dosimetric model for the small intestine was developed that takes into consideration the localization of the radiopharmaceutical in the intestinal wall or in the contents. It also calculates the contribution from self-dose and cross-dose. With this model, more accurate calculations of absorbed dose to radiation-sensitive cells in the intestine are possible.