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Principles of gross alpha and beta radioactivity detection in water.

A simultaneous detection of gross alpha and beta radioactivity was studied using gas proportional counting. This measurement is a part of a method mandated by US Environmental Protection Agency to screen for alpha and beta radioactivity in drinking water. Responses of a gas proportional detector to alpha and beta particles from several radionuclides were determined in drop and electroplated geometries. It is shown that, while the alpha radioactivity can be measured accurately in the presence of beta radioactivity, the opposite is not typically true due to alpha-to-beta crosstalk. The crosstalk, originating from the emission of conversion and Auger electrons as well as x rays, is shown to be dependent primarily on the particular alpha-decay scheme while the dependence on alpha energy is small but negligible. It was measured at 28-35% for 241Am, 22-24% for 230Th, and 4.9-6.5% for 239Pu. For 210Po, the crosstalk of 1.2-1.6% was observed mostly due to energy retardation. A method of reducing the crosstalk to a <3% level is proposed by absorbing the atomic electrons in a 6.2 mg cm(-2) Al absorber, at the same time decreasing the beta efficiency by 16-31%.

Alpha Particles↗

Radioimmunotherapy for acute leukemia.

BACKGROUND: The use of monoclonal antibodies to deliver radioactive isotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native monoclonal antibodies. In this article, we summarize the role of radioimmunotherapy in the treatment of leukemia. METHODS: The authors reviewed the published clinical trials of radioimmunotherapy in acute leukemia. RESULTS: Radioimmunoconjugates that emit beta-particles, such as 131I-anti-CD33, 90Y-anti-CD33, 131I-anti-CD45, and 188Re-anti-CD66c, deliver significant doses of radiation to the bone marrow and may be particularly effective when used as part of a conditioning regimen for hematopoietic stem cell transplantation. Radioimmunoconjugates that emit short-ranged alpha-particles, such as 213Bi-anti-CD33, are better suited for the treatment of low-volume or residual disease. CONCLUSIONS: Radiolabeled antibodies can be administered safely to patients with advanced leukemias and have significant antileukemic activity. Radiolabeled antibodies can potentially intensify the antileukemic effects of conditioning regimens when used in conjunction with hematopoietic stem cell transplantation. Whether or not radiolabeled antibodies improve the outcome of patients with leukemia remains to be demonstrated by randomized studies.

Acute Disease↗

Dose measurement based on spectral chi-square minimization using GAFchromic MD-55 film.

A new method of measuring dose using GAFchromic MD-55-2 type film is proposed. It involves 2D fitting of optical density, as a function of both wavelength and dose, to a set of measured calibration data. An unknown dose to a film can then be determined by minimizing the chi-square between the measured optical densities and the fitted calibration data. The methodology was tested, using 60Co calibration, by measuring the dose deposited in films irradiated by a 32p source in a semi-infinite geometry. The results are compared with the expected dose obtained From beta counting, taking into account the dose loss correction due to various attenuating materials, including the film substrate itself, which was determined to be 20%. It was found that the root mean relative deviation between the measured and expected doses was approximately 3%. The excellent agreement also demonstrated the possibility of calibration between gamma and beta particles.

Beta Particles↗

Electron spectra measurements and Monte Carlo calculations for a 60Co standardised hot particle source.

A benchmark set of measured beta particle spectra for a standardised 60Co hot particle source is presented. The spectra were obtained for conditions similar to those encountered in practical dosimetric applications. The measured spectra were compared with Monte Carlo calculations using the MCNP code. These comparisons provided information to guide the selection of the optimal set-up parameters of the code. Important differences were observed in the MCNP calculated spectra when ITS and the default indexing style algorithm were used. Overall the calculations using the default mode of MCNP version 4B provide the best agreement with the measured electron spectra.

Body Burden↗

A mouse model for calculating cross-organ beta doses from yttrium-90-labeled immunoconjugates.

BACKGROUND: The organs of laboratory mice used in radioimmunotherapy experiments are relatively small compared to the ranges of high-energy yttrium-90 (Y-90) beta particles. Current Medical Internal Radiation Dose (MIRD) dosimetry methods do not account for beta energy that escapes an organ. A dosimetry model was developed to provide more realistic dose estimates for organs in mice who received Y-90-labeled antibodies by accounting for physical and geometric factors, loss of beta dose due to small organ sizes, and cross-organ doses. METHODS: The dimensions, masses, surface areas, and overlapping areas of different organs of 10 athymic nude mice, each weighing approximately 25 g, were measured to form a realistic geometric model. Major organs in this model include the liver, spleen, kidneys, lungs, heart, stomach, small intestine, large intestine, thyroid, pancreas, bone, marrow, and carcass. A subcutaneous tumor mass also was included in the model. By accounting for small organ absorbed fractions and cross-organ beta doses, the MIRD methodology was extended from humans to mice for beta dose calculations. RESULTS: Absorbed fractions of beta energy were calculated using the Berger's point kernels and the electron transport code EGS4. Except for the tumor and carcass, the self-organ absorbed fractions ranged from 15% to 20% in smaller organs (the marrow and thyroid) to 65%-70% in larger organs (the liver and small intestine). Cross-organ absorbed fractions also were calculated from estimates of the overlapping surface areas between organs. CONCLUSION: The mathematic mouse model presented here provides more realistic organ dosimetry of radiolabeled monoclonal antibodies in the nude mouse, which should, in turn, contribute to a better understanding of the correlation of biodistribution study results and organ-tumor toxicity information.

Animals↗

Self-absorption of tritium betas in metal tritide particles.

Inhaling metal tritide particles is a potential occupational hazard. The radiation dose to tissue from tritide particles depends on their solubility and retention in the body. In each tritide particle, a portion of the beta particles from decay of tritium is absorbed by the metal matrix and therefore cannot contribute to absorbed radiation dose to tissue. A theoretical model for estimating the self-absorption of tritium betas in spherical metal tritide particles is presented. Numerical calculations are made with this method for titanium, zirconium, and erbium particles from 0.5 to 50 microm in diameter. The tritium spectrum is divided into energy groups to facilitate estimation of the energy that escapes the particle for dose calculations. Our results show considerable absorption of beta particles and their energy, even for respirable particles smaller than 5 microm. Limited experimental data of self-absorption for titanium and zirconium tritides supported the theoretical calculation. It is concluded that the self-absorption factors should be required for counting tritide particle samples as well as for estimating absorbed radiation dose to tissue.

Absorption↗

Evaluation of the effect of 90Sr beta-radiation on human blood cells by chromosome aberration and single cell gel electrophoresis (comet assay) analysis.

Among various environmental genotoxins, ionizing radiation has received special attention because of its mutagenic, carcinogenic and teratogenic potential. In this context and considering the scarcity of literature data, the objective of the present study was to evaluate the effect of 90Sr beta-radiation on human cells. Blood cells from five healthy donors were irradiated in vitro with doses of 0.2-5.0Gy from a 90Sr source (0.2Gy/min) and processed for chromosome aberration analysis and for comet assay. The cytogenetic results showed that the most frequently found aberration types were acentric fragments, double minutes and dicentrics. The alpha and beta coefficients of the linear-quadratic model, that best fitted the data obtained, showed that 90Sr beta-radiation was less efficient in inducing chromosome aberrations than other types of low linear energy transfer (LET) radiation such as 3H beta-particles, 60Co gamma-rays, 137Cs and 192Ir and X-rays. Apparently, 90Sr beta-radiation in the dose range investigated had no effect on the modal chromosome number of irradiated cells or on cell cycle kinetics. Concerning the comet assay, there was an increase in DNA migration as a function of radiation dose as evaluated by an image analysis system (tail moment) or by visual classification (DNA damage). The dose-response relation adequately fitted the non-linear regression model. In contrast to the cytogenetic data, 90Sr beta-radiation induced more DNA damage than 60Co gamma-radiation when the material was analyzed immediately after exposures. A possible influence of selective death of cells damaged by radiation was suggested.

Adult↗

Experimental determination of 32P dose backscatter factors at and near soft-tissue boundaries.

Beta-ray dose backscatter factors with respect to soft tissue were measured using an extrapolation chamber. The beta-ray dose backscatter factor is a measure of the change effected in absorbed dose to a soft-tissue medium when part of the medium is replaced by a material other than soft tissue (i.e., a scatterer); the source is located at the boundary between the two media. The dependencies of backscatter factor on scatterer atomic number and on source geometry are investigated, and the variation of backscatter factor with distance from the boundary is determined. For a 32P point source, backscatter factors with respect to Mylar, a soft-tissue substitute, at 0.55 mg/cm2 from the boundary, are, 29.65[0.12]%, 31.07[0.24]%, 19.30[0.48]%, 16.27[0.35]%, 5.46[0.11]% and -26.44[0.02]% for bismuth, tungsten, cadmium, copper, aluminum, and air scatterers, respectively. Backscatter factors measured for a 32P planar source are generally smaller than those for a point source. The variation of backscatter factor with distance from the boundary is well represented analytically by sums of exponentials. Therefore, the rate of decrease of backscatter factor with distance can be specified by a relaxation length, defined as the depth through which the backscatter factor is reduced by 1/e, where e is the base of the natural logarithm. For example, with a 32P planar source, relaxation lengths in Mylar are 588[7] mg/cm2 and 238[2]mg/cm2 for bismuth and aluminum scatterers, respectively. Qualitative interpretation of backscatter factor depth profiles is presented. In addition, the variations of backscatter factor with scatterer atomic number and with source geometry are discussed with reference to existing experimental findings on beta particle reflection.

Beta Particles↗

A novel silicon array designed for intraoperative charged particle imaging.

A novel Si-PIN imaging array is under investigation for a charged particle (beta, positron, or alpha) sensitive intraoperative camera to be used for (residual) tumor identification during surgery. This class of collimator-less nuclear imaging device has a higher signal response for direct interactions than its scintillator-optical detector-based counterparts. Monte Carlo simulations with 635 keV betas were performed, yielding maximum and projected ranges of 1.64 and 0.55 mm in Si. Up to 90% of these betas were completely absorbed in the first 0.30 mm. Based on these results, 300 microm thick prototype Si detector arrays were designed in a 16 x 16 crossed-grid arrangement with 0.8 mm wide orthogonal strips on 1.0 mm pitch. A NIM- and CAMAC-based high-density data acquisition and processing system was used to collect the list mode data. The system was calibrated by comparisons of measured spectra to energy deposition simulations or by direct measurement of various >100 keV conversion electron or beta emitters. Mean electronic noise per strip was <3.6 keV FWHM at room temperature. When detecting positrons, which have an accompanying 511 keV annihilation background, the flood irradiated beta/gamma ratio was approximately 40, indicating that beta images could be made without the use of background rejection techniques. The intrinsic spatial resolution corresponds to the 1 x 1 mm2 pixel size, and measurements of beta emitting point and line sources yielded FWHM resolutions of 1.5 (lateral) and 2.5 mm (diagonal), respectively, with the larger widths due to particle range blurting effects. Deconvolution of the finite source size yielded intrinsic resolutions that corresponded to the image pixel size. Transmission images of circle and line phantoms with various hole sizes and pitch were resolved with either pure beta or positron irradiation without a background correction. This novel semiconductor imaging device facilitates high charged particle and low gamma sensitivity, high signal/noise ratio, and allows for compact design to potentially aid surgical guidance by providing in situ images of clinical relevance.

Alpha Particles↗

Glycogen in epidermal nerve terminals of Lacerta sicula (squamata: reptilia).

Proof is given that the granula occuring in the epidermal discoid nerve terminals of Lacerta sicula consist of glycogen. Staining with PA-PbCi shows 300 A sized alpha-particles and 70 A sized beta-particles. The electron-dense boundary appearing after digestion with alpha-amylase consists of limit-dextrins.

Animals↗

The dose absorbed by lymphocytes irradiated in vitro with tritiated water.

A simple method of irradiating cells in vitro with beta particles is to add the beta-emitter to a cell suspension; various dosimetric aspects of this procedure have been investigated. It is shown that, due to the different water content of the various constituents of a blood cell suspension, the average dose D beta absorbed by a certain type of cells for a tritium nominal concentration Co and an irradiation time t is given by D beta(t) = KEnCo eta t. Typical values of the factor eta are calculated for lymphocytes. A series of experiments has demonstrated that whilst the uptake phase has negligible effect on the dose, a significant error may arise during washing-out because a proportion of the activity remains in the cells.

Humans↗

Cytotoxicity of alpha-particle-emitting m-[211At]astatobenzylguanidine on human neuroblastoma cells.

Radioiodinated m-iodobenzylguanidine (MIBG) has been used with only limited success for the treatment of neural crest tumors including neuroblastoma. Use of an MIBG analogue labeled with 211At could be advantageous because of the shorter range and higher linear energy transfer of its alpha-particle emissions compared with the beta-particles emitted by 131I. The potential utility of m-[211At]astatobenzylguanidine for the treatment of neuroblastoma was investigated in vitro using 3 human neuroblastoma cell lines known to take up MIBG [SK-N-SH, SK-N-BE(2C), and SK-SY5Y] and a control line lacking MIBG uptake (SK-N-MC). Maximum binding of m-[211At]astatobenzylguanidine ([211At] MABG) to 5 x 10(5) cells after a 2-h incubation ranged from 61% for SK-N-SH to 1% for SK-N-MC. Using a limiting dilution clonogenic assay, the cytotoxicity for SK-N-SH cells of [211At]MABG was compared with [211At]astatide and no-carrier-added [131I]MIBG. A D0 of 5.8 nCi/ml was calculated for [211At]MABG compared with 482 nCi/ml for [211At] astatide, indicating a more than 80-fold enhanced cytotoxicity for the specifically targeted alpha-particles of [211At]MABG. For [211At]MABG, the D0 corresponded to only 6.4 211At atoms bound/cell compared with 9000 atoms/cell for no-carrier-added [131I]MIBG. The D0 values measured for [211At]MABG treatment of SK-SY5Y, SK-N-BE(2C), and SK-N-MC cells were 50, 5.8, and 11,043 nCi/ml, respectively, corresponding to 7.04, 6.46, and 171.79 211At atoms bound/cell. In conclusion, these results have demonstrated that [211At]MABG is considerably more cytotoxic than [131I]MIBG and that [211At]MABG could have great potential as a radiotherapeutic agent for the treatment of neuroblastoma.

Antineoplastic Agents↗

Spatial dose-rate distribution for an 194Ir point source in water.

The spatial dose-rate distribution arising from a unit activity point source of 194Ir embedded in an infinite water medium has been calculated. These results may prove to be both useful and timely; 194Ir is a beta-particle-emitting radionuclide that is a suitable candidate for radioimmunotherapy, and a means for producing it fairly easily has recently been made available. Calculation of the beta-ray dose-rate distribution is based on a new set of monoenergetic electron dose point kernels which are results from an improved Monte Carlo (ETRAN) calculation. The spatial dose-rate distribution for 32P was also calculated and compared with results from the EGS4-PRESTA and ACCEPT Monte Carlo codes. The ETRAN-based distribution agrees with that from EGS4-PRESTA to within 2% out to 3.6 mm from the source, a distance over which 90% of the source energy is deposited. The ETRAN-based distribution also agrees well with that from ACCEPT between 0.6 and 4 mm from the source; at distances < 0.6 mm, values from ACCEPT are about 6% larger than ones calculated here.

Beta Particles↗

Pirocarbotrat: a new radiopharmaceutical for the treatment of solid tumors--comparative studies in N-nitrosomethylurea-induced rat mammary tumors.

To evaluate the effectiveness of a single intratumoral dose of Pirocarbotrat, a gelatin-protected charcoal suspension labeled with chromic [32P]pyrophosphate, studies of bioelimination, biodistribution and therapeutic action were carried out in rats, and the results obtained were compared with those of other 32P dispersions. We found that 78.3% of the treated tumors reduced size after 32 days of treatment. At that time, the total eliminated activity was 12.70 +/- 3.90% distributed in urine (8.30 +/- 1.80%) and feces (4.40 +/- 3.50%). Biodistribution studies demonstrate that 84.50 +/- 2.60% of the injected activity remained in the tumor, with no significant concentration in the rest of the organism. We conclude that Pirocarbotrat can be used as a safe agent for brachytherapy of solid tumors with beta particles.

Animals↗

Multicellular dosimetry for micrometastases: dependence of self-dose versus cross-dose to cell nuclei on type and energy of radiation and subcellular distribution of radionuclides.

UNLABELLED: In radioimmunotherapy, the treatment of bulk tumors by radionuclides that emit energetic beta particles is the preferred approach. However, for the eradication of small clusters of cancer cells, radionuclides that emit Auger electrons or alpha particles are considered to be advantageous because of their ability to deposit radiation energy locally. If such radionuclides are internalized by the cells, the total dose to the cell nuclei is thought to be primarily determined by the self-dose (dose to cell nucleus from activity within the cell) in comparison to the cross-dose (dose to the cell nucleus from activity in all other cells). METHODS AND RESULTS: The self-dose-to-cross-dose ratios to the cell nucleus were calculated for different cluster sizes (26-400 microns) with monoenergetic electron and alpha particle sources distributed uniformly in different cell compartments (cell surface, cytoplasm, nucleus). Model calculations were also performed for several radionuclides (Auger, beta and alpha emitters). Absorbed fractions for sources of monoenergetic electron and alpha particles, distributed uniformly in small spheres (26-5000 microns), were also calculated along with S-values for a number of radionuclides. CONCLUSIONS: When most of the cells in the cluster are labeled with beta or alpha emitters, the cross-dose component of the total dose is important irrespective of cluster size and subcellular source distribution and increases as the cluster size increases. The self-dose is always important for Auger emitters. When the self-dose is negligible, the mean absorbed dose to the cell nuclei is well represented by the mean dose to the micrometastasis.

Alpha Particles↗

A special mini-extrapolation chamber for calibration of 90Sr+90Y sources.

90Sr+90Y applicators are commonly utilized in brachytherapy, including ophthalmic procedures. The recommended instruments for the calibration of these applicators are extrapolation chambers, which are ionization chambers that allow the variation of their sensitive volume. Using the extrapolation method, the absorbed dose rate at the applicator surface can be determined. The aim of the present work was to develop a mini-extrapolation chamber for the calibration of 90Sr+90Y beta ray applicators. The developed mini-chamber has a 3.0 cm outer diameter and is 11.3 cm in length. An aluminized polyester foil is used as the entrance window while the collecting electrode is made of graphited polymethylmethacrylate. This mini-chamber was tested in 90Sr+90Y radiation beams from a beta particle check source and with a plane ophthalmic applicator, showing adequate results.

Beta Particles↗

Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides.

UNLABELLED: Targeted radionuclide therapy is a new form of radiotherapy that differs in some important respects from external beam irradiation. One of the most important differences is due to the finite range of ionizing beta particles emitted as a result of radionuclide disintegration. The effects of particle range have important implications for the curability of tumors. METHODS: We used a mathematical model to examine tumor curability and its relationship to tumor size for 22 beta-emitting radionuclides that may have therapeutic potential. The model assumed a uniform distribution of radionuclide throughout. RESULTS: For targeted radionuclide therapy, the relationship between tumor curability and tumor size is different from that for conventional external beam radiotherapy. With targeted radionuclides, there is an optimal tumor size for cure. Tumors smaller than the optimal size are less vulnerable to irradiation from radionuclides because a substantial proportion of the disintegration energy escapes and is deposited outside the tumor volume. CONCLUSION: We found an optimal tumor size for radiocurability by each of the 22 radionuclides considered. Optimal cure diameters range from less than 1 mm for short-range emitters such as 199Au and 33P to several centimeters for long-range emitters such as 90Y and 188Re. The energy emitted per disintegration may be used to predict optimal cure size for uniform distributions of radionuclide.

Beta Particles↗

Endovascular beta irradiation for prevention of restenosis using solution radioisotopes: pharmacologic and dosimetric properties of rhenium-188 compounds.

PURPOSE: Irradiation of the arterial wall with beta particles has been shown to be effective in inhibiting neointimal hyperplasia following percutaneous transluminal coronary angioplasty (PTCA). In this study, we describe the use of 188W/188Re generators to obtain 188Re (half-life 16.9 h, maximal beta energy of 2.12 MeV) as a new candidate radioisotope for endovascular irradiation. We have evaluated two [188Re]-compounds as candidates for use as solution-based radiation sources that would allow conventional liquid-filled balloon inflation for delivery of radiation to the vessel wall. While balloon rupture at nominal inflation pressures is a very rare event, (<1 per 10,000 at high pressure), radioisotope release could potentially result in significant dose to radiation-sensitive organs. We have thus evaluated the biodistribution, dosimetry, and kinetics of excretion in rats of two 188Re-labeled compounds that are proposed for intravascular therapy. MATERIALS AND METHODS: Rhenium-188 was obtained as [188Re]-sodium perrhenate by saline elution of an alumina-based 188W/188Re generator system (>500 mCi). High specific volume solutions of the [188Re]-sodium perrhenate (>50 mCi/ml) were obtained by post-elution concentration of the generator bolus by passage through a tandem silver cation/anion column system. Rhenium-188-labeled benzoylthioacetyltriglycine (MAG3) was prepared by stannous ion reduction of [188Re]-perrhenate in the presence of the benzyl-MAG3 substrate, and was characterized as a single radioactive component. Rhenium-188-perrhenate and [188Re]-MAG3 were administered to separate groups of Fischer rats, which were sacrificed at various times and the tissue distribution of 88Re determined in the major organs. Excretory products were also collected daily from separate groups of rats for each agent over 7 days. The effects of perchlorate and iodide preblocking and postdisplacement of thyroid uptake of [188Re]-perrhenate were also evaluated. RESULTS: Organ uptake values were modest for both agents [<0.25 % injected dose(ID)/gram of tissue at 6 h] for all organs evaluated except for the thyroid, with the intestines and intestinal contents showing the highest uptake values (0.72-1.97 %ID/gram). Whereas thyroid uptake of 188Re after injection of [188Re]-MAG3 was low (0.16 %ID/gram), uptake after injection of [188Re]-perrhenate was higher and could be blocked by pretreatment with perchlorate (intravenous [IV]) or displaced by perchlorate posttreatment. Also, oral or IV iodide pre- or postadministration could also significantly block or displace thyroid uptake of [188Re]-perrhenate. Both [188Re] agents were excreted primarily via the urinary bladder. The excretion half-life of [188Re]-perrhenate was about 7 h; in contrast, the [188Re]-MAG3 complex showed 50% excretion in less than 2 h. The large intestines received the most significant adsorbed dose, with values of 2.0 cGy/ mCi for [188Re]-perrhenate and 4.6 x 10(-3) cGy/mCi for [188Re]-MAG3. CONCLUSIONS: Rhenium-188-MAG3 shows more rapid urinary bladder excretion in rats than perrhenate and both agents show low organ uptake. Thyroid uptake of free [188Re]-perrhenate can be blocked or displaced with oral perchlorate administration. For the projected use of [188Re]-MAG3 for balloon inflation required for irradiation of the arterial wall, calculated organ dose values are within acceptable limits in the unlikely event of low pressure balloon rupture. Rhenium-188-MAG3 in solution is thus a new candidate for balloon dilation providing uniform endovascular irradiation following PTCA for restenosis therapy.

Angioplasty, Balloon, Coronary↗