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Comparisons of the efficacy of 186Re- and 131I-labeled antibody in multicell spheroids.

Several radionuclides are being studied for use in radioimmunotherapy. Although 131I has been used most widely, there are several disadvantages to it including its large gamma-ray component, its rather long half-life, and its modest beta-particle energy. However, the beta-particle energy can be an advantage in very small tumors (less than 1-2 mm). 186Re has several potential advantages over 131I but it has never been directly compared with it experimentally. Dosimetry modeling predicted that 186Re would have a dose advantage over 131I at large tumor sizes but for tumors as small as 1 mm diameter, this advantage would be lost. In order to confirm these predictions experimentally, this study compared the relative efficacy of a pancarcinoma antibody, NR-LU-10 labeled with 186Re or 131I in 0.8-1.0 mm diameter LS174T human colon adenocarcinoma multicell spheroids. Spheroids were incubated for 90 hr at 37 degrees C and evaluated with clonogenic assay, autoradiography, and histology. When corrected for cumulative activity bound, both radionuclides were equally effective. Autoradiography demonstrated poor penetration of radionuclide into the depths of the spheroids. Because 186Re has a theoretical dose advantage in larger tumors and because it has been shown to be equivalent to 131I in tumors as small as 1 mm diameter, it may be superior to 131I in most clinical situations. However, in the treatment of micrometastases of less than 1 mm diameter, theoretical dosimetry modeling predicts that 131I or radionuclides with similar beta particle energies should be more effective.

Autoradiography

The ability of ionizing radiations of different LET to induce chromosomal deletions in Aspergillus nidulans.

Conidia, derived from a strain of Aspergillus nidulans known to carry a specific chromosomal duplication, were irradiated. The duplicated segment had genetic markers, which, when eliminated from the genome, allowed the easy detection of deletion mutants. Survival curves derived following 15 MeV electron and gamma-ray irradiation were characterised by the presence of an appreciable shoulder, whilst 50 kvp X-rays gave a much smaller shoulder. Irradiation with beta-particles and alpha-particles gave rise to exponential survival curves. The RBE values for these radiations, based on the D37 value were for gamma-rays, 1.0, 15 MeV electrons 1.0, 50 kvp X-rays 1.9, beta-particles 2.1 and alpha-particles 3.4. With the exception of gamma-rays the radiations described were compared with respect to their ability to induce chromosomal deletions. When the number of deletants amongst survivors was plotted against dose, a linear relationship was found for electrons, X-rays and beta-particles. The response recorded for alpha-particles was essentially linear but with a biphasic component. The RBE values for the radiations, based on a value of unity for 15 MeV electrons were as follows: X-rays 1.3, beta-particles 0.8, alpha-particles above 7.5 krad 2.3 and below 7.5 krad 3.5. When these same data were re-plotted with number of deletants amongst survivors against log survival, electrons appeared the most efficient radiation at producing deletants amongst survivors, with an "m value" of 283 X 10(-5). Tritiated water was least efficient, the corresponding value being 182 X 10(-5). The number of deletants per 10(4) conidia plated, when plotted against dose yielded a curve which increased to a peak and then decreased linearly for all radiations. The peaks for electrons, X-rays and alpha-particles each had a value of about 14 deletants per 10(4) conidia plated and the peaks roughly corresponded with the point at which the survival curve became exponential and was clearly indicative of the accumulation of sub-lethal damage. However, for beta-particles the peak had a value of 7 deletants per 10(4) conidia plated. A non-DNA target has been implicated for cellular death following beta-particle irradiation.

Americium

Synergism between electricity and ionizing radiation.

Weak direct electric currents which produce little (or no) lethal damage to Escherichia coli bacteria are shown to act synergistically with ionizing radiation, both electromagnetic radiation (X-ray) and charged particles (beta radiation). This synergism greatly enhances the lethal effect of ionizing radiation on bacteria. This is possibly due to increased single-strand breaks in DNA, as detected by the alkaline sucrose gradient method. It is also shown that in cells with thymidine-3H incorporated into their DNA and treated with electricity, the radioactivity is released from the acid-insoluble fraction to the acid-soluble fraction, so that the ratio of radioactivity in the soluble fraction to that in the insoluble fraction increases from 0.47 in the non-treated control cells to 3.46 in the cells treated with an electric current of 1.0 mA (3.0 V) for 30 min, which indicates extensive degradation of cellular DNA. No synergism is detected between electricity and 254 nm UV radiation nor between electricity and X-rays, when these two agents are used sequentially in any order. Electricity alone produces lesions in cell membranes, as shown by electron microscopy.

Beta Particles

Expression of vasopressin receptors in hamster hypothalamus is sexually dimorphic and dependent upon photoperiod.

The distribution of vasopressin receptors was studied in the brain of a photoperiodic animal, the Siberian hamster. Attention was focused on [3H]vasopressin binding sites located in the hypothalamic ventromedial nucleus, medial tuberal nucleus, and ventral premammillary nucleus in males or females kept in long or short photoperiod conditions. Displacement experiments with structural analogs suggested that vasopressin receptors in the hamster hypothalamus are of the vasopressor (V1) type. Quantitative data obtained with a gaseous detector of beta-particles indicated that in the ventromedial nucleus and in the ventral premammillary nucleus of animals in long photoperiod, the number of beta-particles emitted per unit area was significantly greater in males than in females. In the ventromedial hypothalamic nucleus, in both males and females, the number of beta-particles emitted was significantly lower in short than in long photoperiod conditions. In the ventral premammillary nucleus, shortening of the photoperiod had a significant effect in reducing the amount of [3H]vasopressin bound in females, but not in males. These data suggest that, in the hamster, the control of the expression of vasopressin receptors differs among various hypothalamic nuclei and may depend on the sex and/or on the level of circulating gonadal steroids.

Animals

External exposure estimates for individuals near the Nevada Test Site.

Individuals living near the Nevada Test Site were exposed to both beta and gamma radiations from fission products and activation products resulting from the atmospheric testing of nuclear devices. These exposures, and the resultant doses, were functions of the amount of material deposited, the time of arrival of the debris, and the amount of shielding afforded by structures. Results are presented for each of nine generic life-styles. These are representative of the living patterns of people residing in the area. For each event at each location for which data exist, a representative of each life-style was closely followed for 30 d. The results of these detailed calculations were then extrapolated to the present, employing a stochastic model. Results displayed are the geometric means and standard deviations derived from 25 independent determinations of the various quantities shown. For each determination, required parameters were randomly selected from appropriate distributions. Calculations yielded estimates for: 1) whole-body and skin dose due to gamma rays from material on the ground; 2) skin dose due to beta particles from material deposited directly on the skin; and 3) skin dose due to beta particles from material deposited on the ground. Organ dose estimates were established from the whole-body dose using appropriate conversion factors. For the homemaker life-style, the uterus dose was also calculated as a function of time for 9 mo. This assisted in estimating fetal dose as a function of gestation.

Beta Particles

Glycogen changes in the liver cells of young rats following isoprenaline treatment. (Histochemical and ultrastructural investigations).

Glycogen changes were investigated by light and electron microscopy in the liver cells of newborn rats following isoprenaline (IPR) treatment either for 1 day (2 intraperitoneal injections at 12 h interval), or for 8 days (2 intraperitoneal injections daily). On the day following the interruption of both treatments glycogen depletion was observed as compared to control rats, as evaluated by PAS reaction and confirmed by higher total phosphorylase activity. During this stage electron microscopy revealed mainly alpha-particles of glycogen associated to highly dilated smooth endoplasmic reticulum (SER) after 1-day-treatment, and to mostly increased SER after prolonged treatment. In the animals submitted to prolonged IPR administration and sacrificed at later times, glycogen masses intensely PAS-positive were strongly increased, while the activity of total phosphorylase proved accordingly lower than in the rats sacrificed at earlier times. Electron microscopy examination confirmed an increased amount of glycogen (alpha- and beta-particles) differently distributed: beta-particles were more numerous in the liver of the rats sacrificed on the last day of the experiment. At this time SER didn't appear modified as compared to control rats.

Animals

Estimates of dose to intraperitoneal micrometastases from alpha and beta emitters in radioimmunotherapy.

Intraperitoneal metastases from ovarian and other gynecologic tumors are a significant source of treatment failure. In recent years, investigators have used radiolabeled monoclonal antibodies to treat this disease with encouraging results. We have developed a dose calculational technique which generates isodose distributions from intraperitoneally administered alpha and beta particle emitters. In this study we apply the calculations to tissue biopsy samples to determine the adequacy of dose to ovarian micrometastases. Tissue samples from staging biopsies at the time of surgical debulking are scanned to identify small metastases. The patient population studied comprised those with ovarian disease who based on clinical criteria would be considered good candidates for intraperitoneal radioimmunotherapy. The regions of interest (which include the tumor and surface of the peritoneum) are digitized and tumor volumes are contoured. Dose calculations based on the modeling of intraperitoneally administered antibodies radiolabeled with various isotopes is performed and the minimum dose to tumor and normal tissue is assessed. For example, with tumor uptake of 0.1% injected dose per gram of tissue, the surface tumor dose from alpha emitters is up to 45,000 rads. The dose falls to 6000 rads at approximately 40 microns from the peritoneal surface. The surface dose from 20 mCi 90Y administered in 1500 ml saline is up to 10,000 rads, and at a 2-mm depth, approximately 2000 rads. From our calculation dose distribution from radioimmunotherapy varies as a function of physical characteristics of the isotope, absorption of activity, and amount of disease being treated.

Alpha Particles

Ordered synthesis and mobilization of glycogen in the perfused heart.

The molecular order of synthesis and mobilization of glycogen in the perfused heart was studied by 13C NMR. By varying the glucose isotopomer ([1-13C]glucose or [2-13C]glucose) supplied to the heart, glycogen synthesized at different times during the perfusion was labeled at different carbon sites. Subsequently, the in situ mobilization of glycogen during ischemia was observed by detection of labeled lactate derived from glycolysis of the glucosyl monomers. When [1-13C]glucose was given initially in the perfusion and [2-13C]glucose was given second, [2-13C]lactate was detected first during ischemia and [3-13C]lactate second. This result, and the equivalent result when the glucose labels were given in the reverse order, demonstrates that glycogen synthesis and mobilization are ordered in the heart, where glycogen is found morphologically only as beta particles. Previous studies of glycogen synthesis and mobilization in liver and adipocytes [Devos, P., & Hers, H.-G. (1979) Eur. J. Biochem. 99, 161-167; Devos, P., & Hers, H.-G. (1980) Biochem. Biophys. Res. Commun. 95, 1031-1036] have suggested that the organization of beta particles into alpha particles was partially responsible for ordered synthesis and mobilization. The observations reported here for cardiac glycogen suggest that another mechanism is responsible. In addition to examining the ordered synthesis and mobilization of cardiac glycogen, we have selectively monitored the NMR properties of 13C-labeled glycogen synthesized early in the perfusion during further glycogen synthesis from a second, differently labeled substrate. During synthesis from the second labeled glucose monomer, the glycogen resonance from the first label decreased in integrated intensity and increased in line width.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

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 curability of tumours of differing size by targeted radiotherapy using 131I or 90Y.

A mathematical model has been used to investigate the relationship of curability to tumour size and cell number for spherical tumours treated with targeted 131I or 90Y, assuming uniform uptake of radionuclide throughout the tumour. The analysis shows that, for any given cumulated activity per unit mass of tumour, cure probability is greatest for tumours whose diameter is close to an optimum value which depends on the path length of the emitted beta-particle. Smaller tumours are less curable because of inefficient absorption of radiation energy, and larger tumours are less curable because of greater clonogenic cell number. The lesser curability of very small tumours is a feature of targeted radiotherapy using long-range beta-emitters which does not occur with external beam irradiation. The predicted inefficiency of sterilisation of microscopic tumours poses a problem for targeted radiotherapy which is analogous to "geographic miss" in conventional radiotherapy. The implication is that small micro-metastases could escape sterilisation by radionuclides administered at activity levels sufficient to eradicate larger tumours. It is suggested that single agent targeted radiotherapy should not be used for treatment of disseminated malignancy when multiple tumours of differing size, including micrometastases, may be present. The analysis implies that an advantage might result from the use of a panel of several radionuclides (including short-range emitters) or from combining targeted radiotherapy using long-range beta-emitters with external beam irradiation or some other modality to which microscopic tumours are preferentially vulnerable.

Beta Particles

Simulation of angular and energy distributions of the PTB beta secondary standard.

Calculations and measurements have been performed to assess radiation doses delivered by the PTB Secondary Standard that employs 147Pm, 204Tl, and 90Sr:90Y sources in prescribed geometries, and features "beam-flattening" filters to assure uniformity of delivered doses within a 5-cm radius of the axis from source to detector plane. Three-dimensional, coupled, electron-photon Monte Carlo calculations, accounting for transmission through the source encapsulation and backscattering from the source mounting, led to energy spectra and angular distributions of electrons penetrating the source encapsulation that were used in the representation of pseudo sources of electrons for subsequent transport through the atmosphere, filters, and detectors. Calculations were supplemented by measurements made using bare LiF TLD chips on a thick polymethyl methacrylate phantom. Measurements using the 204Tl and 90Sr:90Y sources revealed that, even in the absence of the beam-flattening filters, delivered dose rates were very uniform radially. Dosimeter response functions (TLD:skin dose ratios) were calculated and confirmed experimentally for all three beta-particle sources and for bare LiF TLDs ranging in mass thickness from 10 to 235 mg cm-2.

Beta Particles

Ultrastructure of the different fibre types in axial muscles of the sharks Etmopterus spinax and Galeus melastomus.

Red, intermediate and white axial muscle fibres of the sharks Etmopterus spinax and Galeus melastomus were studied by electron microscopy and morphometry. The mitochondrial content is more than thirty percent in red, less than one percent in white, and up to fifteen percent in intermediate fibres. About one third of the mitochondria in red fibres are accumulated close to the sarcolemma. Red fibres contain much glycogen, present as rosettes (alpha particles). Intermediate fibres contain less glycogen (as beta particles). White fibres have scarcely any visible energy reserves. Red fibres contain slightly less (4-5%) of the sarcotubular system than the other fibre types (6-8%). In all fibre types, the terminal cisternae of the SR are regularly divided by clefts. Triads or dyads are generally positioned at the Z discs, but in Galeus white fibres two dyads may be present, one on each side of the Z disc. The morphology is discussed in relation to current views on the functions of different muscle fibre types.

Animals

Sources of Atomic and Nuclear Data for Biomedical Purposes.

Users of nuclear and atomic data for biomedical purposes often have difficulty in identifying the most up-to-date and appropriate sources of such data. The biomedical Subcommittee of the UK Nuclear Data Committee have prepared a list of recommended data sources available at the beginning of 1978 on radioactive decay schemes; neutron cross-sections and data for neutron activation analysis; excitation functions for the production of radionuclides by charged particles; W-values for neutron and electron dosimetry; X- and gamma-ray cross-sections; stopping powers and ranges for charged particles; and dose deposition by electrons and beta particles.

Alpha Particles

Absorbed doses to skin from radionuclide sources on the body surface.

Beta-particle and electron doses are reported for radionuclides on the skin surface. Upper and lower bounds on doses are based on Monte Carlo calculations that include or exclude electron scattering in air, respectively. Upper bounds agree well with results of point-kernel calculations performed by others.

Absorption

A single TLD dose algorithm to satisfy federal standards and typical field conditions.

Modern whole-body dosimeters are often required to accurately measure the absorbed dose in a wide range of radiation fields. While programs are commonly developed around the fields tested as part of the National Voluntary Accreditation Program (NVLAP), the actual fields of application may be significantly different. Dose algorithms designed to meet the NVLAP standard, which emphasizes photons and high-energy beta radiation, may not be capable of the beta-energy discrimination necessary for accurate assessment of absorbed dose in the work environment. To address this problem, some processors use one algorithm for NVLAP testing and one or more different algorithms for the work environments. After several years of experience with a multiple algorithm approach, the Dosimetry Services Group of Yankee Atomic Electric Company (YAEC) developed a one-algorithm system for use with a four-element TLD badge using Li2B4O7 and CaSO4 phosphors. The design of the dosimeter allows the measurement of the effective energies of both photon and beta components of the radiation field, resulting in excellent mixed-field capability. The algorithm was successfully tested in all of the NVLAP photon and beta fields, as well as several non-NVLAP fields representative of the work environment. The work environment fields, including low- and medium-energy beta radiation and mixed fields of low-energy photons and beta particles, are often more demanding than the NVLAP fields. This paper discusses the development of the algorithm as well as some results of the system testing including: mixed-field irradiations, angular response, and a unique test to demonstrate the stability of the algorithm. An analysis of the uncertainty of the reported doses under various irradiation conditions is also presented.

Algorithms

EGS4 Monte Carlo determination of the beta dose kernel in water.

The EGS4 Monte Carlo code has been used to simulate the emission and energy deposition in H2O about point sources of monoenergetic electrons and radionuclides of potential use in radioimmunotherapy. The radiations studied were 0.05, 0.1, 0.5, 1.0, 2.0, and 3.0 MeV monoenergetic electrons and 32P, 67Cu, 90Y, 105Rh, 131I, 153Sm, 186Re, and 188Re beta particles and conversion and Auger electrons. Ten batches of 10,000 electrons (or 10,000 radionuclide decays) each were started isotropically at a point in an infinite homogeneous H2O phantom. The parameter-reduced electron-step transport algorithm (PRESTA) version of the EGS4 Monte Carlo code was used to follow these and their progeny, scoring the energy deposited in thin spherical shells. The scaled dose kernels are calculated and compared to kernels available in the literature. These previously published kernels either completely ignore secondary electrons or are based on a Monte Carlo code which improperly sampled the Landau energy straggling distribution.

Beta Particles

A special pattern of the smooth endoplasmic reticulum in the kidney of the snail Cryptomphalus aspersa.

A special structural pattern of the smooth endoplasmic reticulum (SER) has been observed in the kidney of the snail Cryptomphalus aspersa. Two types of cells (clear and dark) cover the foldings of the renal sac; the dark cells are by far the most numerous. A cisterna of SER enveloping the nucleus appears invariably in both types of cells, with no disruptions, or small ones (from 50 to 90 nm) along its profile. The layer of cytoplasm lodged between the external nuclear membrane and this cisterna is found invariably to be from 0-20 to 0-25 mum in width. Glycogen is abundant in the cytoplasm as alpha particles, and also in the nucleus, but as beta particles. It is noteworthy that absolutely no glycogen is present in the layer of cytoplasm lodged between the nuclear membrane and the surrounding SER envelope. Long profiles of SER are also observed closely approaching and parallel to the plasma membrane of the dark cells. Considering the role of SER in glycogen metabolism in the kidney of the snail, the possible function of these cisternae as a support system ofr enzymes involved in the metabolism of glucides is discussed.

Animals