Optimisation study of alpha-cyclotron production of At-211/Po-211g for high-LET metabolic radiotherapy purposes.

The production of no-carrier-added (NCA) alpha-emitter (211)At/(211g)Po radionuclides for high-LET targeted radiotherapy and immunoradiotherapy, through the (209)Bi(alpha,2n) reaction, together with the required wet radiochemistry and radioanalytical quality controls carried out at LASA is described, through dedicated irradiation experiments at the MC-40 cyclotron of JRC-Ispra. The amount of both the gamma-emitter (210)At and its long half-lived alpha-emitting daughter (210)Po is optimised and minimised by appropriate choice of energy and energy loss of alpha particle beam. The measured excitation functions for production of the main radioisotopic impurity (210)At-->(210)Po are compared with theoretical predictions from model calculations performed at ENEA.

On the high-resolution gamma-ray spectrometric measurement of 40K in natural and synthetic materials.

Many regulatory agencies require that all building materials and industrial waste be tested for their naturally occurring radioactive material (NORM) concentrations before they can be used or thrown away. Usually the NORM concentrations of 40K, 232Th and 238U are measured by gamma-ray spectrometry using high-purity germanium or NaI(Tl) detectors. 40K is measured through its 1460.8 keV gamma line, which is mixed with 1459.2 keV line of 228Ac from the chain of 232Th. This fact ignored till now, requires a correction in the computation of 40K concentration. Although in many cases the error is <1%, there are cases where there have been higher errors. It should be emphasised that even if the correction in 40K concentration is large, the correction of the external dose index is negligible owing to the weighing factor being higher for 232Th than for 40K (by at least a factor of 10).

Secondary neutron and photon dose in proton therapy.

BACKGROUND AND PURPOSE: The dose due to secondary neutrons and photons in proton therapy was estimated with Monte Carlo simulations. Three existing facilities treating eye and deep-seated tumours were taken into account. The results of the calculations related to eye proton therapy were verified with measurements. MATERIALS AND METHODS: The simulations were performed with the FLUKA code. Neutron fluence was measured inside an Alderson phantom (type ART) with activation techniques. RESULTS: The maximum dose due to secondaries produced in a passive beam delivery system was estimated to be of the order of 10(-4) and 10(-2) Gy per therapy Gy for eye and deep tumour treatments, respectively. In the case of irradiations of deep-seated tumours carried out with an active system, the dose was of the order of 10(-3) Gy per therapy Gy. CONCLUSIONS: The dose due to secondaries depends on the geometry of the beam delivery system and on the energy of the primary beam and is lower in the healthy tissues distant from the target volume.

Environmental biochemistry of current environmental levels of heavy metals: preparation of radiotracers with very high specific radioactivity for metallobiochemical experiments on laboratory animals.

Environmental toxicology research on dose-response relationships of heavy metals requires experiments on laboratory animals exposed to "low doses" of trace elements which should reflect "present or actual environmental levels" characteristic of polluted environments. Unfortunately no criteria exist to establish the "low doses" to which laboratory animals must be exposed, in practice the choice of the level used is made in an almost arbitrary manner. In order to define the "present environmental levels" of heavy metals which should be administered to laboratory animals an approach is suggested, based upon knowledge of the concentrations of trace elements in the diet, air and food as well as the fractions absorbed. Today daily intakes of trace elements by man are of the order of few micrograms or nanograms thus requiring the use of extremely sensitive analytical techniques to determine the very low amounts of heavy metals in tissues and cellular components. In these fields of research the use of radiotracers with very high specific radioactivity appears particularly advantageous but requires considerable care during their preparation and use. The first part of this paper deals with a definition of the ranges of concentrations of trace elements which should be used for metabolic studies on laboratory animals when they are exposed via different routes such as ingestion, inhalation in injection; the second part describes the production of radiotracers with very high specific radioactivity by proton activation in the cyclotron and by neutron irradiation in the nuclear reactor. Their use to label present levels of heavy metals under conditions adapted for biochemical purposes, as well as the preparation of different metal-labelled chemical species is also reported. Particular attention is directed to quality control of the radiotracer solutions which are administered to the animals including those of radioactivity concentrations, radioisotopic purity, radiochemical purity, carrier content and chemical impurities.

Content of trace elements in the respirable fractions of the air particulate of urban and rural areas monitored by neutron activation analysis.

The concentrations (ng/m3) of more than 30 trace elements have been determined in the total air particulate matter and in the size-segregated fractions collected in urban, industrialized, and rural residential areas in northern Italy by means of a multistage inertial impactor with the PM10 inlet. All measurements have been carried out by instrumental neutron activation analysis, except for Pb and Cd, which have been determined by electrothermal atomic absorption spectroscopy. Analytical quality assurance procedures have been developed with special regard to blanks, reagents, and sampling. Total concentrations and the granulometric distribution found in the different locations are reported and compared.

Neutron spectrum measurements at a 40-MeV proton cyclotron.

A set of seven activation reactions has been selected for neutron spectral analysis in the environment of a proton-cyclotron target. This choice of reactions: 59Co(n, p) 59Fe, 59Co(n, 2n) 58Co, 59Co(n, 3n) 57Co, 197Au(n, gamma) 198Au, 197Au(n, 2n) 196Au, 197Au(n, 4n) 194Au, 27Al(n, alpha) 24Na, analyzed by means of a Ge(Li) detector, reduces to a minimum of three the number of activation detectors employed, and makes possible convenient and accurate spectral measurements to at least 40 MeV. Criteria for selection of the activation materials from a list of candidates are discussed. A detailed comparison of the unfolding programs LYRA and SAND is made, and reasons are given for our choice of SAND in our application. Spectra of neutrons emitted at 0 degrees, 45 degrees and 90 degrees from thick targets of A1, Fe, Cu, Ta and stainless steel, irradiated by 40-MeV protons at the Milan AVF cyclotron, using the analysis technique described, are given and discussed.

Neutron measurements in the stray field produced by 158 GeV c(-1) per nucleon lead ion beams.

This paper discusses measurements carried out at CERN in the stray radiation field produced by 158 GeV c(-1) per nucleon 208Pb82+ ions. The purpose was to test and intercompare the response of several detectors, mainly neutron measuring devices, and to determine the neutron spectral fluence as well as the microdosimetric (absorbed dose and dose equivalent) distributions in different locations around the shielding. Both active instruments and passive dosimeters were employed, including different types of Andersson-Braun rem counters, a tissue equivalent proportional counter, a set of superheated drop detectors, a Bonner sphere system, and different types of ion chambers. Activation measurements with 12C plastic scintillators and with 32S pellets were also performed to assess the neutron yield of high energy lead ions interacting with a thin gold target. The results are compared with previous measurements and with measurements made during proton runs.

Phantom dosimeters examined by NMR analysis: a promising technique for 3-D determinations of absorbed dose.

Fricke-infused agarose gels examined by nuclear magnetic resonance (NMR) analysis are inspected, and their response to gamma-rays, thermal neutrons and protons, at radiotherapy dose levels, is examined. The gel composition is chosen with attention to the tissue equivalence for the radiation fields of interest; this problem is crucial, in particular, for thermal neutrons. The feasibility of three-dimensional determination of absorbed dose in Fricke-gel phantoms is investigated, and the possibility of employing the technique in conformal therapies, such as boron neutron capture therapy (BNCT) and proton therapy, is tested. Isodose curve determination in a cylindrical gel phantom exposed to thermal neutrons is presented. A method for depth-dose profiling in tissue exposed to protons is described, and some results are reported which show that the depth-dose data are determinable with millimetric precision. Results obtained with a spectrophotometer from gel augmented with a metal indicator are reported and discussed also. These results show the possibility of obtaining a very sensitive dosimetry technique consisting of spectrophotometric analysis of such a Fricke-gel.

Influence of the chemical form on the plasma clearance of ruthenium in humans.

The radioisotopes of ruthenium (103Ru and 106Ru) are abundant fission products and represent a radiological risk for the population in case of nuclear accidents. Few biokinetic studies have been performed on humans up to now and consequently the current model recommended by ICRP for ruthenium is derived mainly by extrapolation from animal data. The stable isotope 101Ru and proton activation analysis have been used to study the biokinetics of Ru in blood plasma samples taken during 8 studies in three healthy volunteers. The results obtained demonstrated that complexed Ru (in the form of citrate Ru(IV) complexes) is cleared from blood plasma very rapidly (characteristic half time of 17+/-2 min), while inorganic Ru remains longer in the systemic circulation, and is transferred to other organs and/or excreted with a biological half time of 23+/-2h. Good reproducibility of the clearance curves indicated no evidence of inter- or intra-individual variability when the same Ru solution was injected in repeated experiments to different subjects.

A re-evaluation of the biokinetics of zirconium in humans.

There is much interest in understanding the biokinetics of zirconium in humans due to the potential radiological risk represented by the radionuclide 95Zr and by its daughter 95Nb. Despite the significance of zirconium, few data are available on the actual biokinetics of zirconium in humans. Accordingly the biokinetic model currently recommended by ICRP for this element is based mainly on data from animal experiments. In this study, the use of the stable isotopes 90Zr and 96Zr as tracers has enabled the conduct of 6 biokinetic investigations in 3 healthy volunteers. These studies have provided new valuable information about intestinal absorption and kinetics in blood plasma of zirconium and have been used for the set-up of a more realistic compartmental model with possible applications for dosimetric purposes.

Fricke gel dosimetry in boron neutron capture therapy.

Gel dosimetry allows three-dimensional (3D) measurement of absorbed dose in tissue-equivalent dosemeter phantoms. Gel phantoms are imaged using optical techniques. In neutron capture therapy (NCT), properly designed gel dosemeters can give 3D dose distributions, due to the various components of the secondary radiation, in phantoms exposed in the thermal or epithermal column of a nuclear reactor. In addition to the therapeutic dose arising from the reaction 10B(n,alpha)7Li, the other dose components are also obtainable, i.e. the gamma dose (due to reactor background and to the reaction 1H(n,gamma)2H of thermal neutrons with hydrogen, the dose due to protons emitted in the reaction 14N(n,p)14C of thermal neutrons with nitrogen and the dose due to recoil protons resulting from elastic scattering of epithermal neutrons.

Study of a method based on TLD detectors for in-phantom dosimetry in BNCT.

A method has been developed, based on thermoluminescent dosemeters (TLD), aimed at measuring the absorbed dose in tissue-equivalent phantoms exposed to thermal or epithermal neutrons, separating the contributions of various secondary radiation generated by neutrons. The proposed method takes advantage of the very low sensitivity of CaF2:Tm (TLD-300) to low energy neutrons and to the different responses to thermal neutrons of LiF:Mg,Ti dosemeters with different 6Li percentage (TLD-100, TLD-700, TLD-600). The comparison of the results with those obtained by means of gel dosemeters and activation foils has confirmed the reliability of the method. The experimental modalities allowing reliable results have been studied. The glow curves of TLD-300 after gamma or neutron irradiation have been compared; moreover, both internal irradiation effect and energy dependence have been investigated. For TLD-600, TLD-100 and TLD-700, the suitable fluence limits have been determined in order to avoid radiation damage and loss of linearity.

Stable tracer investigations in humans for assessing the biokinetics of ruthenium and zirconium radionuclides.

The interest in the biokinetics of ruthenium and zirconium in humans is justified by the potential radiological risk represented by their radionuclides. Only a few data related to the biokinetics of ruthenium and zirconium in humans are available and, accordingly, the biokinetic models currently recommended by the ICRP for these elements are mainly based on data from animal experiments. The use of stable isotopes as tracers, coupled with a proper analytical technique (nuclear activation analysis with protons) for their determination in biological samples, represents an ethically acceptable methodology for biokinetic investigations, being free from any radiation risk for the volunteer subjects. In this work, the results obtained in eight biokinetic investigations for ruthenium, conducted on a total of three healthy volunteers, and six for zirconium, performed on a total of three subjects, are presented and compared to the predictions of the ICRP models.

Biomedical applications of cyclotrons and review of commercially available models.

The growing use of cyclotrons in biomedicine, both for clinical and research purposes and in particular for the production of short-lived radionuclides which are extremely useful in nuclear medicine diagnosis, has reached a stage in which commercial companies are able to offer several models with different performances, in order to satisfy the demand of different users. Many of these commercially produced accelerators are installed all over the world and some of them have been operating for several years, demonstrating that this category of machine has reached a high degree of reliability. A brief description of the operating principle of the cyclotron is presented, together with an illustration of its possible applications in the medical field. A list of the models presently available on the market is given and the installation problems and the criteria to be followed in the choice of a model are discussed. Finally, likely future developments in the field are briefly discussed.

[Cyclotrons in medicine. A survey of commercial models and their biomedical applications]. / Il ciclotrone in medicina. Una rassegna dei modelli commerciali e delle loro applicazioni biomediche.

At present in Italy there is a great interest in the use of cyclotrons for medical applications: according to a plan of CNR (National Research Council), accelerators of this kind are going to be installed in some hospitals. After the explanation of the cyclotron operation principles, an outline is given of the possible applications with particular care for the clinical ones. An up-to-date review of commercial models so far developed is reported and finally, after a short note concerning installation problems, some suggestions are given about criteria to be followed in the choice of a model, according to the foreseen scientific program.

Similarity in metabolic patterns of different chemical species of vanadium in the rat.

To gain information about the influence of the oxidation state of vanadium on its metabolic behavior, different 48V-labeled vanadium compounds, such as cationic VO2+(V), VO2+(IV), V3+(III), and anionic V4O12(3-)(V), VS4(3-)(V) species were prepared and intravenously injected into rats. The 48V radioactivity was measured in whole tissues as well as in nuclei, mitochondria, lysosomes, microsomes, and cytosols from liver and kidney homogenates. The distribution of 48V radioactivity between the plasma components was investigated using gel filtration of the 48V-labeled plasma. The findings indicate that there are common pathways of the different chemical forms of vanadium in animals. The similarities are referred to the distribution in different tissues and their intracellular distribution as well as to the transport in the blood, in which 48V was always found in the plasma bound to transferrin. The results obtained tend to exclude a possible influence of the oxidation state of vanadium on its metabolism and support the existence in the body of two mechanisms of conversion of different chemical forms of vanadium ions to one with the same valence.

Energy deposition by proton beams of up to 31 MeV in microscopic volumes.

The frequency distributions of energy deposition in microscopic volumes for proton beams of various energies and energy spreads were determined by means of a "rossi type" proportional counter. Tissue equivalent spherical volumes of 0.6, 0.72, 0.80, 1.00, 1.25, 1.50, 1.75, 2.00 micrometer diameter were simulated. Frequency distributions of energy deposition per unit pathlength are reported and their behavior as a function of the simulated pathlength, beam energy and energy spread is discussed. The results indicate that energy deposition distributions in microscopic volumes for protons in the range 8-31 MeV are skewsymmetric distributions with a tail on the high energy side, and that degraded beams behave differently from monoenergetic ones. Dose mean lineal energy values have been quoted for beams used in radiobiological experiments.