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Chiral beta-particles interact differentially with enantiomers--theory to solve a long-existing debate.

The crucial organic molecules associated with life are chiral. Beta irradiation on the causal origin for the great preference of biomolecules in life over their corresponding enantiomers has been extensively studied. The left helical beta electrons, with spin and momentum antiparallel, should propagate with different velocities in the two enantiomers. Much effort has been done to investigate possible mechanism of inducing asymmetry, using longitudinally polarized beta rays to decompose asymmetrically racemic mixtures of biomolecules, but the results were inconclusive and contradictory. In this paper we present our viewpoint that the direct inelastic scattering between polarized electrons and chiral molecules is the dominant one in producing the asymmetry of cross sections for both beta+ and beta- irradiation. The inelastic cross section sigma (0 --> n) is dependent on the dipole strength Dn, rotatory strength Rn of the molecule. According to the theoretical study, the asymmetry of cross section F is approximately 10(-6) and it depends on the sign of Rn+(L type). When Rn+ > 0, sigma D > sigma L, it favors L-amino acid surviving. When Rn+ < 0, sigma D < sigma L, it favours D-amino acid surviving. Our results show that helical electrons do distinguish between molecules of opposite chirality, and the disputation and suspicion about the controversial experimental results between Garay and Darge & Thiemann can be explained.

Amino Acids↗

Experimental and computational techniques for beta-particle dosimetry.

This paper reports the experimental and the computational techniques that were specifically developed to provide dose response data for a new method of beta dosimetry, which is reported in an accompanying article (Sh87). The specific experimental techniques consist of setting up, calibrating and obtaining backscattering and resolution corrections for a plastic-scintillator-based beta spectrometer. The computation techniques involve (1) adapting a Monte Carlo electron transport computer code to use measured beta energy distributions as input data and (2) using the code to calculate the energy deposition of these distributions of electrons in a slab of material. The energy deposition of backscattered electrons incident on the slab is also taken into account. Codes, which were developed to calculate the energy deposited by photons in LiF, are used to derive a theoretical value for the TLD response calibration factor. This factor compares well to the experimentally derived result which was obtained by exposing TLDs to a calibrated 137Cs/137mBa photon source.

Algorithms↗

Cellular effects of beta-particle delivery on vascular smooth muscle cells and endothelial cells: a dose-response study.

BACKGROUND: Although endovascular radiotherapy inhibits neointimal hyperplasia, the exact cellular alterations induced by beta irradiation remain to be elucidated. METHODS AND RESULTS: We investigated in vitro the ability of 32P-labeled oligonucleotides to alter (1) proliferation of human and porcine vascular smooth muscle cells (VSMCs) and human coronary artery endothelial cells (ECs), (2) cell cycle progression, (3) cell viability and apoptosis, (4) cell migration, and (5) cell phenotype and morphological features. beta radiation significantly reduced proliferation of VSMCs (ED50 1.10 Gy) and ECs (ED50 2.15 Gy) in a dose-dependent manner. Exposure to beta emission interfered with cell cycle progression, with induction of G0/G1 arrest in VSMCs, without evidence of cell viability alteration, apoptosis, or ultrastructural changes. This strategy also proved to efficiently inhibit VSMC migration by 80% and induce contractile phenotype appearance, as shown by the predominance of alpha-actin immunostaining in beta-irradiated cells compared with control cells. CONCLUSIONS: 32P-labeled oligonucleotide was highly effective in inhibiting proliferation of both VSMCs and ECs in a dose-dependent fashion, with ECs showing a higher resistance to these effects. beta irradiation-induced G1 arrest was not associated with cytotoxicity and apoptosis, thus demonstrating a potent cytostatic effect of beta-based therapy. This effect, coupled to that on VSMC migration inhibition and the appearance of a contractile phenotype, reinforced the potential of ionizing radiation to prevent neointima formation after angioplasty.

Angioplasty, Balloon, Coronary↗

A comparison of intravascular source designs based on the beta particle emitter 114mIn/114In. Line source versus stepping source.

BACKGROUND: Catheter-based intravascular brachytherapy (IVB) sources of the next generation will have to meet high demands in terms of miniaturization, flexibility, safety, reliability, costs and versatility. The radionuclide pair 114mIn/114In (half-life 49.51 days, maximum beta energy 2.0 MeV, average beta energy 0.78 MeV) is an attractive beta emitter for application in such a source. METHODS: Since metallic indium is unfit for the manufacture of a brachytherapy source, the feasibility, safety and dosimetric properties of a design concept comprising a linear array of ceramic In2O3 spheres within a thin-walled, superelastic Ni/Ti capsule are investigated. RESULTS: Neutron activation of enriched In2O3 spheres yields a specific activity sufficiently high for the manufacture of a stepping source, keeping treatment times limited to a few minutes. Although 114mIn/114In also emits some gamma radiation, the effective doses received by members of the medical staff are an order of magnitude lower than those received from fluoroscopy. The dose distributions about a 40-mm line source and a 5-mm stepping source (outer diameter 0.36 mm) are calculated using MCNP4C. Dose-volume histograms (DVHs) are calculated for the line source (centered and noncentered) and the stepping source (centered) using the geometry of a human coronary artery. CONCLUSION: The results show that a centered stepping source with optimized dwell times delivers the most homogenous dose within the target volume.

Angioplasty, Balloon, Coronary↗

Matrix metalloproteinases-3, -7, and -12, but not -9, reduce high density lipoprotein-induced cholesterol efflux from human macrophage foam cells by truncation of the carboxyl terminus of apolipoprotein A-I. Parallel losses of pre-beta particles and the high affinity component of efflux.

Matrix metalloproteinases (MMPs) have been suggested to function in remodeling of the arterial wall, but no information is available on their possible role in early atherogenesis, when cholesterol accumulates in the cells of the arterial intima, forming foam cells. Here, we incubated the major component responsible for efflux of cholesterol from foam cells, high density lipoprotein 3 (HDL(3)), with MMP-1, -3, -7, -9, or -12 at 37 degrees C before adding it to cholesterol-loaded human monocyte-derived macrophages. After incubation with MMP-3, -7, or -12, the ability of HDL(3) to induce the high affinity component of cholesterol efflux from the macrophage foam cells was strongly reduced, whereas preincubation with MMP-1 reduced cholesterol efflux only slightly and preincubation with MMP-9 had no effect. These differential effects of the various MMPs were reflected in their differential abilities to degrade the small pre-beta migrating particles present in the HDL(3) fraction. NH(2)-terminal sequence and mass spectrometric analyses of the apolipoprotein (apo) A-I fragments generated by MMPs revealed that those MMPs that strongly reduced cholesterol efflux (MMPs-3, -7, and -12) cleaved the COOH-terminal region of apoA-I and produced a major fragment of about 22 kDa, whereas MMPs-1 and -9, which had little and no effect on cholesterol efflux, degraded apoA-I only slightly and not at all, respectively. These results show, for the first time, that some members of the MMP family can degrade the apoA-I of HDL(3), so blocking cholesterol efflux from macrophage foam cells. This expansion of the substrate repertoire of MMPs to include apoA suggests that these proteinases are directly involved in the accumulation of cholesterol in atherosclerotic lesions.

Apolipoprotein A-I↗

Calibration and characterization of beta-particle sources for intravascular brachytherapy.

The calibration of a catheter-based system to be used for therapeutic radiation treatment to prevent restenosis following interventional coronary procedures is described. The primary dosimetry was performed ionometrically using an extrapolation chamber equipped with a 1-mm diameter collecting electrode to measure absorbed dose in tissue equivalent plastic at a depth of 2 mm. These results are compared with measurements with radiochromic dye film, which is also used to characterize sources for axial and trans-axial uniformity, and to determine dose distributions at various depths. A protocol for dose calculation based on that of AAPM TG43 is suggested for these sources, and examples of its use are given for the calculation of the enhancement effect on dose rate from a single seed source due to neighboring seeds. Monte Carlo calculations were also performed to validate the measured results.

Beta Particles↗

Accounting for beta-particle energy loss to cortical bone via paired-image radiation transport (PIRT).

Current methods of skeletal dose assessment in both medical physics (radionuclide therapy) and health physics (dose reconstruction and risk assessment) rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model which provides a more realistic three-dimensional (3D) geometry for particle transport in the skeletal site at both microscopic and macroscopic levels of its histology. Ex vivo CT scans were acquired of the pelvis, cranial cap, and individual ribs excised from a 66-year male cadaver (BMI of 22.7 kg m(-2)). For the three skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were taken and subjected to microCT imaging. Voxels within the resulting microCT images were then segmented and labeled as regions of bone trabeculae, endosteum, active marrow, and inactive marrow through application of image processing algorithms. The PIRT methodology was then implemented within the EGSNRC radiation transport code whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the CT microimage of the skeletal site. At initial electron energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow are noted between PIRT model simulations and those estimated under existing techniques of infinite spongiosa transport. Calculations of radionuclide S values under both methodologies imply that current chord-based models may overestimate the absorbed dose to active bone marrow in these skeletal sites by 0% to 27% for low-energy beta emitters (33P, 169Er, and 177Lu), by approximately 4% to 49% for intermediate-energy beta emitters (153Sm, 186Re, and 89Sr), and by approximately 14% to 76% for high-energy beta emitters (32p, 188Re, and 90Y). The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow-containing bones within the skeleton thus permitting improved estimates of absorbed fractions and radionuclide S values for intermediate-to-high energy beta emitters.

Aged↗

Photobinding of [gamma-(32)P] ATP gamma-benzophenone to the surface of a polyurethane membrane in the preparation of a beta-particle-emitting balloon catheter.

PURPOSE: The goal of this study was to photochemically bind 5'-[gamma-(32)P]-azido-ATP gamma-benzophenone ((32)P-ATP-BPA) to a polyurethane surface. Expandable balloon catheters composed of (32)P-coated polyurethane have the potential for preventing restenosis following percutaneous transluminal coronary angioplasty. METHODS: After extensive preparation and cleaning of polyurethane disks, 10 microL of the radioactive ATP-BPA reagent (specific activity = 9.4 Ci/mmol) was applied to the surface. After drying, the membrane disks were exposed ultraviolet radiation (254 nm; 6,000 microwatts/cm(2)) for up to 2 h and subsequently washed. The amount of (32)P bound to the membrane disks was determined by Cerenkov counting in a liquid scintillation counter. The effect of the labeling solution composition (solvent, presence of potassium or manganese ions, addition of surfactants, etc.) on photobinding efficiency was determined. RESULTS: The efficiency of attaching the (32)P-ATP-BPA reagent to the polyurethane surfaces was markedly dependent upon the cleaning and pretreatment conditions. Following detailed washing and rinsing steps, a photobinding efficiency of 36.4+/-3.6% was obtained with 10 min UV exposure time using (32)P-ATP-BPA solutions that were 95/5 methanol/water by vol. Increasing the concentration of the (32)P-ATP-BPA reagent did not improve the photobinding efficiency; however, the total amount of (32)P bound to the disks was increased. CONCLUSIONS: Photochemical methods can be employed to attach beta(-)-emitting radionuclides to polymers that are employed as balloon catheters. The preparation of the polymeric material (washing, rinsing, and drying) is critically important in maximizing the amount of (32)P-ATP-BPA that can be bound to the polymer.

Adenosine Triphosphate↗