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Absorbed doses for internal radiotherapy from 22 beta-emitting radionuclides: beta dosimetry of small spheres.

We calculated the mean absorbed fractions, specific absorbed fractions and mean doses per unit of cumulated activity in source spheres 10 microm-2 cm in radius for 22 beta-emitting radionuclides potentially useful in radioimmunotherapy. We considered two models of radionuclide distribution, either uniform at the surface of the source or throughout its volume. For each model, we calculated both the absorbed fractions in the spherical segments composing the source and the mean absorbed fractions. For surface distribution, we calculated the mean dose per unit of cumulated activity for a concentric sphere with a small radius (5 microm) in order to determine the minimal dose delivered to the target. Calculations were performed using point kernels for monoenergetic emissions and then integrated into the beta spectra of the different emitters (32p, 33p, 47Sc, 67Cu, 77As, 90Y, 105Rh, 109Pd, 111Ag, 121Sn, 131I, 142Pr, 143Pr, 149Pm, 153Sm, 159Gd, 166Ho, 177Lu, 186Re, 188Re, 194Ir and 199Au). Monoenergetic emissions were taken into account. Results are reported in the form of tables to facilitate use during dosimetric studies for radioimmunotherapy. An application is presented showing the potential utility of associating emitters with different energies in order to sterilize a range of tumour targets of variable size.

Algorithms↗

Treatment planning for radio-immunotherapy.

To foster the success of clinical trials in radio-immunotherapy (RIT), one needs to determine (i) the quantity and spatial distribution of the administered radionuclide carrier in the patient over time, (ii) the absorbed dose in the tumour sites and critical organs based on this distribution and (iii) the volume of tumour mass(es) and normal organs from computerized tomography or magnetic resonance imaging and appropriately correlated with nuclear medicine imaging techniques (such as planar, single-photon emission computerized tomography or positron-emission tomography). Treatment planning for RIT has become an important tool in predicting the relative benefit of therapy based on individualized dosimetry as derived from diagnostic, pre-therapy administration of the radiolabelled antibody. This allows the investigator to pre-select those patients who have 'favorable' dosimetry characteristics (high time-averaged target: non-target ratios) so that the chances for treatment success may be more accurately quantified before placing the patient at risk for treatment-related organ toxicities. The future prospects for RIT treatment planning may yield a more accurate correlation of response and critical organ toxicity with computed absorbed dose, and the compilation of dose-volume histogram information for tumour(s) and normal organ(s) such that computing tumour control probabilities and normal tissue complication probabilities becomes possible for heterogeneous distributions of the radiolabelled antibody. Additionally, radiobiological consequences of depositing absorbed doses from exponentially decaying sources must be factored into the interpretation when trying to compute the effects of standard external beam isodose display patterns combined with those associated with RIT.

Beta Particles↗

A model for dose estimation in therapy of liver with intraarterial microspheres.

Therapy with intraarterial microspheres is a technique which involves incorporation of radioisotope-labelled microspheres into a capillary bed of tumour and normal tissue. Betaemitters such as 90Y and 166Ho are used for this purpose. This technique provides tumour to normal tissue (TNT) dose ratios in the range of 2-10 and demonstrates significant clinical benefit, which could potentially be increased with more accurate dose predictions and delivery. However, dose calculations in this modality face the difficulties associated with nonuniform and inhomogeneous activity distribution. Most of the dose calculations used clinically do not account for the nonuniformity and assume uniform activity distribution. This paper is devoted to the development of a model which would allow more accurate prediction of dose distributions from microspheres. The model calculates dose assuming that microspheres are aggregated into randomly distributed clusters, and using precomputed dose kernels for the clusters. The dose kernel due to a microsphere cluster was found by numerical integration of a point source dose kernel over the volume of the cluster. It is shown that a random distribution of clusters produces an intercluster distance distribution which agrees well with the one measured by Pillai et al in liver. Dose volume histograms (DVHs) predicted by the model agree closely with the results of Roberson et al for normal tissue and tumour. Dose distributions for different concentrations and types of radioisotope as well as for tumours of different radii, have been calculated to demonstrate the model's possible applications.

Beta Particles↗

The investigation of different cameras for in-beam PET imaging.

In situ and in vivo treatment plan verification and beam monitoring as well as dose control during heavy-ion tumour therapy can be performed in principle by measurements of range distributions of beta(+)-emitting nuclei by means of PET techniques. For this purpose the performance of different types of positron camera as well as the results of in-beam PET experiments using beams of beta(+)-active heavy ions (15O, 17F and 19Ne with energies of 300-500 A MeV) are presented. Following the deduced performance requirements a PET scanner that is designed for clinical use in experimental heavy-ion therapy at GSI Darmstadt has been built. This limited angle tomograph consists of two large-area detector heads based on position sensitive BGO detectors and is predicted to perform the measurement of the end point of a beta(+)-emitting ion beam for the verification of a treatment plan with a precision better than 1 mm. The maximum dose applied in the patient thereby is of the magnitude of 10 mGy.

Beta Particles↗

Electron beam dose calculations with the VMC algorithm and the verification data of the NCI working group.

The accuracy of the Monte Carlo algorithm for fast electron dose calculation, VMC, is demonstrated by comparing calculations with measurements performed by a working group of the National Cancer Institute (NCI) of the USA. For both energies investigated, 9 and 20 MeV, the measurements in water are taken to determine the energy spectra of the Varian Clinac 1800 accelerator. For the majority of the experiments a good agreement is found between measurements and VMC calculations. However, in some cases deviations have been observed, which could be explained by the incompletely known geometry on the one hand and by inconsistent data on the other hand. As a reference, dose distributions calculated by the MDAH pencil-beam algorithm are also presented. It is shown that, especially near low- or high-density inhomogeneities, large dose overestimations and underestimations are calculated by using a pencil-beam approach, whereas VMC is able to reproduce the correct doses for these cases also.

Algorithms↗

Calculation of the dose distribution in water from 71Ge K-shell x-rays.

The dose distribution in water from 71Ge K-shell x-rays (Eave = 9.44 keV) was calculated for various source configurations using both analytic and EGS4 Monte Carlo calculations. The point source kernel and the buildup factor are presented. The buildup factor for a point source in water has been found to increase up to about 1.1 as radial distance approaches 1 cm. Comparison between 71Ge and 90Sr/Y shows a similarity between their relative dose distribution in water. The dose distribution from a disc source was calculated using the EGS4 code and compared with the results from analytic calculation. Excellent agreement was observed, confirming the validity of analytic calculations. The dose rate at 0.01 cm from a 71Ge disc source was calculated to be about 1.3 x 10(-5) Gy MBq-1 s-1. Based on the results from this study, 71Ge activity of the order of 3.7 x 10(10) Bq (approximately 1 Ci) might be necessary to obtain dose rates typical of 90Sr/Y ophthalmic applicators. The possibility of using 71Ge as a source of radioactive stents was also investigated. A 71Ge stent was modelled as a cylindrical shell source and the dose rates were determined by Monte Carlo calculations. Some calculated results are compared with published values for a 32P-coated stent. The dose rate at 0.01 cm from a 71Ge stent has been calculated to be about 6.5 x 10(-3) Gy MBq-1 h-1, which is much lower than the reported dose rate at the same distance from a 32P-coated stent. However, an initial source activity of the order of 3.7 x 10(7) Bq (approximately 1 mCi) would easily result in a typical target dose (approximately 24 Gy) needed for intravascular stent applications. In conclusion, 71Ge sources could be used as alternatives to beta sources and, unlike high-energy (approximately MeV) beta sources, may provide easily predictable dose distributions in heterogeneous media and low dose rates, which might be beneficial for some clinical applications.

Beta Particles↗

Monte Carlo calculations of the dose backscatter factor for monoenergetic electrons.

Recently, there has been growing interest in beta emitters for therapeutic uses, especially in connection with so-called endovascular (or intravascular) brachytherapy. Since accurate dose estimation is necessary for the success of such applications, some problems in beta-ray dosimetry need further study. Among these problems, we have investigated the effect of electron backscattering on dose, which has significance not only for accurate dose estimation but also for new source design. In this study, an empirical measure of electron backscattering, known as the dose backscatter factor, was calculated using EGS4 Monte Carlo calculations for monoenergetic electrons and various scattering materials. Electron energies were 0.1, 0.5, 1.0, 2.0 and 3.0 MeV in combination with Al (Z = 13), Ti (Z = 22), Sr (Z = 38), Ag (Z = 47) and Pt (Z = 78) scatterers. The dose backscatter factor ranged from 10% to 60%, depending on electron energy and material, and was found to increase with the atomic number Z by a log(Z + 1) relationship. A method is presented for calculating the beta-ray dose backscatter factors using the results of this study. To demonstrate the efficacy of this method, a dose backscatter factor depth profile for 32P near a water/aluminium interface was calculated and these calculated results were found to generally reproduce the depth profile obtained from direct EGS4 calculations using the 32P spectrum. The data presented in this study can be used to calculate dose backscatter factors for any combination of beta emitter/scatterer whose atomic number ranges from 13 to 78.

Beta Particles↗

The use of GAFchromic film to determine the absolute activity of beta emitters.

A method of using GAFchromic film to determine the absolute activity of beta emitters by immersing the film in a bath of activity is described. This includes calculations of the effect of part of the radioactive solution being displaced by the film that is performing the measurement. Calculations have been performed for 90Y, 32P and 188Re. It is shown that for the film used in this study, this effect will cause a correction of the order of 15-20% for the three radionuclides studied. The results of the GAFchromic film measurement are compared with results obtained from liquid scintillation counting and from a commercial dose calibrator. It is shown that for 32P all methods were in reasonable agreement, but for 188Re, although the GAFchromic film and the liquid scintillation counting methods give similar results, the dose calibrator measurement differed by more than 20%. The GAFchromic film was also used to perform a direct measurement of the radiation dose at a distance of 0.5 mm from the surface of a cylindrical source of 188Re activity. This gave good agreement with the value of the dose predicted from theoretical calculations.

Beta Particles↗

The performance of a CCD digital autoradiography imaging system.

Autoradiography is a widely used technique for imaging trace quantities of radioactivity within biological samples, conventionally using photographic film. This method produces images with high spatial resolution, but it suffers from very low sensitivity and poor dynamic range. Digital autoradiography systems with greatly improved sensitivity and linearity are commercially available, but the spatial resolution is usually much less than that achieved using film. We report here the design, construction and characterization of a novel digital autoradiography system based on scientific-grade charged coupled devices (CCDs). Images of x-ray and beta emissions from radionuclides commonly used in autoradiography show that the system can perform high-speed quantitative imaging with a spatial resolution of approximately 30, microm. Using a frame by frame acquisition method the dynamic range is shown to be at least three orders of magnitude. The absolute detection efficiency is comparable to the best of the currently available digital systems. CCD images of 125I and 14C radioisotope distributions in tissue samples are superior to the equivalent film images and have been acquired in 1-10% of the time.

Animals↗

Electron capture radioactive sources for intravascular brachytherapy: a feasibility study.

The feasibility of electron capture (EC) radionuclides as an alternative to the beta and high-energy gamma emitters presently in use for intravascular brachytherapy is investigated. A potential advantage of the low-energy x-ray radiation from EC isotopes may be an enhanced biological effectiveness with respect to the presently applied beta nuclides, but at the same time avoiding the shielding problems induced by the large penetrability of high-energy gamma rays. A survey considering the most important practical aspects such as dose delivery to the vessel walls in reasonable time spans, absorption properties, possible production of sources with the required specific activities and radiation safety reveals 71Ge as the most promising candidate.

Angioplasty, Balloon, Coronary↗

First images of a digital autoradiography system based on a Medipix2 hybrid silicon pixel detector.

We present the first images of beta autoradiography obtained with the high-resolution hybrid pixel detector consisting of the Medipix2 single photon counting read-out chip bump-bonded to a 300 microm thick silicon pixel detector. This room temperature system has 256 x 256 square pixels of 55 microm pitch (total sensitive area of 14 x 14 mm2), with a double threshold discriminator and a 13-bit counter in each pixel. It is read out via a dedicated electronic interface and control software, also developed in the framework of the European Medipix2 Collaboration. Digital beta autoradiograms of 14C microscale standard strips (containing separate bands of increasing specific activity in the range 0.0038-32.9 kBq g(-1)) indicate system linearity down to a total background noise of 1.8 x 10(-3) counts mm(-2) s(-1). The minimum detectable activity is estimated to be 0.012 Bq for 36,000 s exposure and 0.023 Bq for 10,800 s exposure. The measured minimum detection threshold is less than 1600 electrons (equivalent to about 6 keV Si). This real-time system for beta autoradiography offers lower pixel pitch and higher sensitive area than the previous Medipix1-based system. It has a 14C sensitivity better than that of micro channel plate based systems, which, however, shows higher spatial resolution and sensitive area.

Autoradiography↗

Validation of the EGS usercode DOSE3D for internal beta dose calculation at the cellular and tissue levels.

Internal radiotherapy is currently focusing on beta emitters such as 90Y or 131I because of their high-energy emissions. However, conventional dosimetric methods (MIRD) are known to be limited for such applications. They are unable to take into account microscopic radionuclide distribution because standardized anthropomorphic phantoms are used, and absorbed dose is calculated at the organ level. New tools are therefore required for dose assessment at cellular and tissue level (10-100 microm). The purpose of this study was to validate, at this scale, a Monte Carlo usercode (DOSE3D), based on the MORSE combinatorial geometry package and the EGS code system. Dose point-kernel calculations in water were compared to those published by Cross et al and Simpkin and Mackie. They confirm that DOSE3D is a reliable tool for cellular dosimetry in various geometric configurations.

Beta Particles↗

Calibration and validation of a quality assurance system for 90Sr/90Y radiation source trains.

A quality assurance system (OPTIDOS, PTW-Freiburg) developed for dose rate verification of 90Sr/90Y radiation source trains (RSTs) was calibrated and validated. These source trains are used in the 5-F-BetaCath system (Novoste Corp.) for the treatment of endovascular diseases. The calibration factor of the OPTIDOS system was obtained empirically and is valid for 90Sr/90Y dose rate measurements at the specification point which is located at 2 mm distance from the source axis. A total of 187 OPTIDOS dose rate verifications of the 5-F-BetaCath system were performed in different hospitals. The histogram of the deviation between the manufacturer's dose rate specification and the dose rate measured using the OPTIDOS dosimetry system is Gaussian shaped with +/- 3% relative width and a mean shift of about +2% with respect to the corresponding dose rate specification. Additionally, 128 OPTIDOS dose rate verifications of the new jacketed RST (3.5-F-BetaCath, Novoste Corp.) were performed using the same calibration factor as derived for the 5-F-BetaCath system. Distribution of the deviation between the certified and the measured dose rate is nearly identical in comparison to the histogram of the 5-F-BetaCath system. The mean value of the deviations is shifted by -1.5% with respect to the certified dose rate. In order to compare the results of the calibrated OPTIDOS dosimetry system with a standard measuring method, separate dose rate measurements were performed using electron accelerator calibrated radiochromic films in which calibration is traceable to PTB (Physikalisch Technische Bundesanstalt, Germany). Deviation between both the methods is less than 3.1%. These results confirm that the calibrated OPTIDOS dosimetry system can be considered suitable for quality assurance of both types of RST used in the BetaCath systems.

Beta Particles↗

Dose backscatter factors for selected beta sources as a function of source, calcified plaque and contrast agent using Monte Carlo calculations.

Electron backscattering is a prominent secondary effect in beta dosimetry, and is closely correlated with factors such as the geometries of the source and the scattering material, as well as the composition of the scattering material. Previous results were varied depending on the experimental setup and detector resolution, and were generally performed for monoenergetic electron beams, which makes direct application of these factors to beta sources difficult. In this work, backscattering factors were calculated with MCNP 4C for selected beta sources currently in use (32P and 90Sr/90Y) as well as for sources of potential therapeutic use (45Ca, 142Pr and 185W). Specifically, the calculations used beta spectra generated by the SADDE MOD2 code. The factors were calculated as a function of the distance from the interface between water and scatterers. The scatterers include source surroundings, source supporting materials and contrast agents commonly used for imaging purposes in brachytherapy. The results were fit by a simple function for future incorporation into a dose point kernel code. Due to the high-Z material content (iodine, Z = 53) in the contrast agent, a significant dose backscatter was observed near the water interface. Different cross-section algorithms in the MCNP code (inherent and ITS 3.0) affect the factor calculations. The results generated by the ITS 3.0 algorithm closely matched the EGS4 calculations for 32P. The dependence of backscatter factors on log(Z + 1) (Baily 1980 Med. Phys. 7514-9) was observed for all the beta sources with a high correlation coefficient, R (> 0.95). The overall results indicate that the backscattering effect is significant at short distances from the surface of the interface between water and the scattering material. This model can also aid in choosing a source support or mixing materials for beta brachytherapy sources.

Beta Particles↗

Performance measurements of a high-spatial-resolution YAP camera.

Physical properties of a position-sensitive camera for the analysis of biodistributions of gamma- and beta-emitting radiopharmaceuticals in small animals have been studied, in order to achieve optimal operating conditions. The camera consisted of a highly segmented yttrium-aluminate perovskite (YAP) scintillator, coupled to a position-sensitive photomultiplier. The energy resolution, the detection efficiency, the spatial resolution, the spatial linearity and the count-rate linearity of the YAP camera have been determined. Images related to initial activity levels and successive biodistribution evolution in mice organs are presented as an illustration of the camera performance.

Aluminum↗

A theoretical investigation into post-operative, intracavitary beta therapy of high-grade glioblastomas using yttrium-90.

Beta therapy with yttrium-90 (90Y) has recently been introduced as a post-operative intra-cavitary treatment for malignant glioblastoma, a generally radioresistant tumour for which cure rates with conventional radiotherapy are usually very disappointing. This short theoretical study investigates the conditions under which 90Y treatment might be most effective and assesses the likely amounts of activity which must be infused in order to successfully cope with the low radiosensitivities which characterize such tumours. The radiobiological and physical analysis is investigated using the linear quadratic (LQ) model and a range of possible scenarios for the distribution and density of the tumour cells surrounding the surgically formed cavities are considered. The results suggest that, in the absence of diffusion of 90Y from the cavity, the activity typically required for 50% tumour cure is well over 40 mCi (1480 MBq), this being considerably more than the clinically determined activities which may be tolerated. Suggestions are provided for improving the versatility of the model.

Apoptosis↗

Implementation of an electronic personal dosimetry system (EPD) at Oldbury-on-Severn power station.

This article presents the implementation of an electronic personal dosemeter (EPD) as a film badge replacement at Oldbury-on-Severn power station, which is the first major site to use an approval issued by the UK Health and Safety Executive (HSE) for dose measurement by an EPD. The practicalities and history behind the introduction of an EPD for personal dosimetry are described.

Beta Particles↗