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Purpose: To calculate the absorbed fraction (AF) of low energy electrons in small tissue-equivalent spherical volumes by Monte Carlo (MC) track structure simulation and assess the influence of phase (liquid water versus density-scaled water vapor) and of the continuous-slowing-down approximation (CSDA) used in semi-analytic calculations. Methods: An event-by-event MC code simulating the transport of electrons in both the vapor and liquid phase of water using appropriate electron-water interaction cross sections was used to quantify the energy deposition of low-energy electrons in spherical volumes. Semi-analytic calculations within the CSDA using a convolution integral of the Howell range-energy expressions are also presented for comparison. Results: The AF for spherical volumes of radii from 10-1000 nm are presented for monoenergetic electrons over the energy range 100-10,000 eV and the two Auger-emitting radionuclides (125)I and (123)I. The MC calculated AF for the liquid phase are found to be smaller than those of the (density scaled) gas phase by up to 10-20% for the monoenergetic electrons and 10% for the two Auger-emitters. Differences between the liquid-phase MC results and the semi-analytic CSDA calculations are up to approximately 55% for the monoenergetic electrons and up to approximately 35% for the two Auger-emitters. Conclusions: Condensed-phase effects in the inelastic interaction of low-energy electrons with water have a noticeable but relatively small impact on the AF for the energy range and target sizes examined. Depending on the electron energies, the semi-analytic approach may lead to sizeable errors for target sizes with linear dimensions below 1 micron. Int J Radiat Biol

Journal URL: http://www.sciencedirect.com/science/journal/0168583X

Detailed-history Monte-Carlo code is used to study the energy deposition from proton and alpha particle tracks at the sub-cellular level. Inelastic cross sections for both the vapour and liquid phases of water have been implemented into the code in order to explore the influence of non-linear density effects associated with the condensed-phase cellular environment. Results of energy deposition and its straggling for 0.5 to 5 MeV amu(-1) protons and alpha particles traversing or passing near spherical volumes of 2-200 nm in diameter relevant to DNA- and chromosome-size targets are presented. It is shown that the explicit account of delta-ray transport reduces the dose by as much as 10-60%, whereas stochastic fluctuations lead to a relative uncertainty ranging from 20% to more than 100%. Protons and alpha particles of the same velocity exhibit a similar delta-ray effect, whereas the relative uncertainty of the alphas is almost half that of protons. The effect of the phase is noticeable (10-15%) mainly through differences on the transport of delta-rays, which in liquid water have higher penetration distances. It is expected that the implementation of such results into multi-scale biophysical models of radiation effects will lead to a more realistic predictions on the efficacy of new radiotherapeutic modalities that employ either external proton beam irradiation or internal alpha-emitting radionuclides. Radiat Prot Dosimetry

Track-size distributions were measured for chemically etched CR-39 foils exposed to monoenergetic neutrons with energies ranging from 0.144 to 19 MeV and to various broad-spectrum neutron sources including spontaneous fission neutrons from (238)Pu. These tracks are due to energetic charged particles resulting from interactions of the neutrons with the CR-39. The tracks are visible with an optical microscope after chemical etching and vary in size and configuration depending on the particle, energy and angle of incidence. The foils were analysed using an automatic analysis system that scans the foils, identifies valid tracks and records the track-size parameters. The track-size distributions vary with neutron energy for the monoenergetic sources and with the hardness of the broad-spectrum sources. The distribution from the (238)Pu fission source is readily distinguishable from the other sources measured and from distributions owing to the background. Radiat Prot Dosimetry

Delivery of therapeutics (drugs, radionuclides or genes) in vivo can be optimized when carried by a targeting delivery vehicle such as a surfactant vesicle, polymeric micelle or other polymer-coated colloidal particulate. In the present communication, we propose a general method based on self-assembly principles, to construct lipid-polymer bilayer vesicles whose featured characteristics may be altered according to the polymer molecule used, thus be easily designed along the needs of a particular delivery application. Polymer molecules containing non-polymerizable (polypropylene) and polymerisable (methacrylate) hydrophobic groups were used to construct lipid-polymer vesicles by following two different methods of preparation. In accord with our previous findings, when both types of polymer molecules are added to pre-formed liposomes, only weak adsorption onto the lipid surface occurs. Preparation of the vesicles by pre-mixing the lipid and polymer molecules has proved essential in order to allow the hydrophobic blocks of the copolymers to participate as integral parts of the bilayer. Anchoring of a polymerisable polymer onto the lipid bilayer by hydrophobic interactions, resulted in steric stabilization of the vesicles. When UV polymerization of the bilayer-incorporated [Methyl(PEG)2000MA] polymer was induced, inter-vesicle fusion was triggered. Direct cryo-EM imaging of fusion between the PEG-coated liposomes has been observed. Such sterically stabilised fusogenic vesicles were constructed as potential triggered-release delivery systems, responsive to a variety of external stimuli depending on the type of polymerisable, hydrophobic group in the polymer molecule. By altering the properties of the incorporated hydrophobic group, liposomes able to fuse in response to initiators milder than UV light, such as green or red light, sound, temperature, oxygen or pH can be engineered. Faraday Discuss

The ability to determine particle type and energy plays an important role in the dosimetry of heavy charged particles (HCP) and neutrons. A new approach to radiation dosimetry is presented, which is shown to be capable of particle type and energy discrimination. This method is based on utilising radiation induced changes in the digital information stored on three-dimensional optical random access memories (3D ORAM). 3D ORAM is a small cube (a few mm3) composed of poly(methyl methacrylate) doped with a photochromic dye. and it was originally proposed as a memory device in high speed parallel computers. A Nd:YAG laser system is used to write and read binary information (bits) on the ORAM, which functions as a charged particle detector. Both the read and the write processes use two laser beams that simultaneously strike the material to cause a colour change at their intersection (similar to the darkening of light-sensitive sunglasses when exposed to sunlight.) The laser produces colour changes in the ORAM, which then reverts to the original colour ('bit-flips') at sites where energy is deposited from interaction with incident HCP or neutron-recoil protons. The feasibility of this approach was demonstrated both theoretically and experimentally. Calculations based on track structure theory (TST) predict that when HCP interact with the ORAM material, the local energy deposition is capable of inducing measurable 'bit-flips'. These predictions were recently confirmed experimentally using two types of ORAM systems, one based on spirobenzopyran and the other on anthracene, as the photochromic dyes. Radiat Prot Dosimetry

A dosimetric analysis has been performed to evaluate the potential of liposome systems as carriers of radionuclides in internal radiotherapy. METHODS: Pharmacokinetic data for a variety of liposome constructs (multilamellar vesicles [MLV]; small unilamellar vesicles [SUV]; and sterically stabilized liposomes, monosialoganglioside [G(M1)]-coated) were used to obtain tumor and normal-organ absorbed dose estimates for (67)Cu, (188)Re, (90)Y, and (131)I. Dosimetry was performed for two tumor models: subcutaneous Ehrlich ascites tumor, growing intramuscularly, and C26 colon carcinoma, growing intrahepatically. Dose estimates were obtained using the MIRD schema. Tumor doses were obtained assuming local deposition of electron energy; photon contributions were incorporated assuming spheric tumor geometry. With the conservative assumption that intravenously administered liposomes achieve rapid equilibration with the red marrow extracellular fluid volume, red marrow absorbed dose estimates were obtained from blood kinetics. RESULTS: For intramuscular tumors, absorbed dose ratios for tumor to red marrow ranged from 0.93 ((131)I-MLV) to 13.9 ((90)Y-SUV). Tumor-to-liver ratios ranged from 0.08 ((188)Re-MLV) to 0.92 ((188)Re-SUV); corresponding values for tumor to spleen were 0.13 ((90)Y-MLV) and 0.54 ((188)Re-G(M1)). The optimal combination of radionuclide and liposome system was obtained with (90)Y-SUV. Tumor-to-liver ratios for the G(M1)-coated construct were greatest when the tumor was intrahepatic (1.13 for (90)Y). For a given liposome system, absorbed dose ratios for tumor to normal tissue exhibited up to a twofold variation depending on the radionuclide selected. CONCLUSION: This study provides a dosimetric evaluation for the use of some liposome systems as carriers in targeted radionuclide therapy. Although much further work must be undertaken before any clinical application is considered, these results suggest that radionuclide targeting using liposomes is feasible and may have the advantage of reduced red marrow absorbed dose. J Nucl Med