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Distribution of lithium in the rat brain after a single administration known to elicit aversive effects.

In order to get insight into the brain areas involved in the initial unpleasant effects resulting from the administration of lithium (Li+), its distribution was mapped in the rat brain using the 6Li(n,alpha)3H nuclear reaction after a single injection of 6Li2SO4 at doses and latencies corresponding to the elicitation of such unpleasant effects. An improved method for visualization and measurement of local Li+ concentrations was used consisting in diffracting light along the tracks left by alpha particles in a dielectric detector. The distribution of Li+ was found less homogeneous than when Li+ was administered chronically. Periaqueductal and periventricular structures were the brain areas containing the highest concentrations of Li+.

Animals↗

Effectiveness of Cf 252-neutrons at low dose rates.

Californium-252, an isotope emitting neutrons, gamma photons and alpha particles, is being investigated for its practical use in interstitial Curie therapy. After an introduction in which the history of Californium-252 and its application in industry are described, a review of results concerning RBE values of Cf-neutrons for tolerance of different types of normal tissues and for responses of experimental tumors as a function of dose rate is given. In addition, a review of clinical results is presented.

Animals↗

Astatine-211: its possible applications in cancer therapy.

The cyclotron-produced radiohalogen, 211At, is eminently suitable as a possible therapeutic radionuclide. It decays by the emission of 6.8 MeV mean energy alpha-particles, which from a radiobiological viewpoint are of near optimal therapeutic LET. This paper reviews developments in the possible application of [211At]astato-labelled molecules as potential anti-tumour agents. Additionally, radio-dosimetric evidence is presented, and its implications for human cancer therapy are discussed.

Animals↗

Chemical processing for production of no-carrier-added selenium-73 from germanium and arsenic targets and synthesis of L-2-amino-4-([73Se]methylseleno) butyric acid (L-[73Se]selenomethionine).

The Ge(4He, xn) and 75As(p, 3n) reactions were compared as the best potential routes for routine production of selenium-73 (73Se) for medical applications. With 26 MeV alpha particles, available with compact cyclotrons, the first reaction required an enriched 70Ge target of sodium metagermanate to give a production yield of 1 mCi/microAh (0.037 GBq/microAh) in a 105 mg/cm2 target. With 55 MeV protons the As(p, 3n) reaction on natural arsenic yielded 20 mCi/microAh (0.74 GBq/microAh) in a 685 mg/cm2 target. A simple method was developed and optimized for both targets in order to isolate and purify the no-carrier-added selenium in the elemental form with a radiochemical yield greater than 75% in less than 90 min. An automated radiochemical processing unit has been designed for the routine production of 100-150 mCi (3.7-5.5 GBq) batches of carrier-free 73Se ready for radiopharmaceutical labeling. 30 mCi (1.11 GBq) (EOS) of L-2-amino-4-([73Se]methylseleno) butyric acid (L-[73Se]selenomethionine) ready for injection with a specific activity of 5 Ci/mmol (185 GBq/mmol) (EOS) were obtained through a fast chemical synthesis. Radiation absorbed dose estimates for L-[73Se]selenomethionine have been determined. A value of 0.70 rem/mCi (0.19 mSv/MBq) administered was calculated for the risk from irradiation in man. The first human PET investigation with [73Se]selenomethionine showed a very good delineation between liver and pancreas.

Arsenic↗

Applied principles of radiopharmaceutical use in therapy.

The initial consideration in use of a radiopharmaceutical in therapy is specificity of localization. A variety of biological principles such as active transport and binding to cellular components have been utilized to achieve this localization. The next concern is to maximize radiation to the lesion while minimizing that to the remainder of the body. This means that there is a major role to be played by emissions with a short path length (such as alpha particles, weak beta particles and Auger electrons). To achieve maximal irradiation of the lesion, dissociation of the radiolabel from the tissue should be minimized; potential approaches for achieving this are reviewed. Finally, "synergistic effects" between radiation and chemical agents are discussed.

Antibodies, Monoclonal↗

Astatine (211At) as a therapeutic radionuclide. The plasma:blood cell distribution in vitro.

Therapy of carcinoma of the thyroid may include the use of the radionuclide 131I, which localizes to thyroid tissue. In considering the use of another halogen, the alpha particle emitting radionuclide astatine, 211At, there is also the requirement that it too can be taken up by the thyroid. However, in view of its short half-life (7.2 h) it is important that its transport in the blood is not a factor likely to render it less available. For example, retention of 211At by red cells may retard its uptake by the thyroid. This in vitro investigation of the partitioning of the 211At between erythrocytes and plasma indicates that it is not strongly bound by the red cells in blood.

Animals↗

Boron neutron capture irradiation: setting up a clinical programme in Nice.

Neutron capture irradiation aims to selectively destroy tumor cells using 10B(n,alpha)7Li nuclear reactions produced within themselves. Following the capture reaction, an alpha particle and a, 7Li ion are emitted. Carrying an energy of 2.79 MeV, they destroy all molecular structures along their path close to 10 microns. These captures, used exclusively with a 'slow' neutron irradiation, provide a neutron capture therapy (BNCT). If they are used in addition to a fast neutron beam irradiation, they provide a neutron capture potentiation (NCP). The Centre Antoine-Lacassagne in Nice is actively involved in the European Demonstration Project for BNCT of grade IV glioblastomas (GBM) after surgical excision and BSH administration. Taking into account the preliminary results obtained in Japan, work on an 'epithermal' neutron target compatible with various cyclotron beams is in progress to facilitate further developments of this technique. For NCP, thermalized neutron yield has been measured in phantoms irradiated in the fast neutron beam of the biomedical cyclotron in Nice. A thermal peak appears after 5 cm depth in the tissues, delayed after the fast neutron peak at 1.8 cm depth. Thus, a physical overdosage of 10% may be obtained if 100 ppm of 10B are assumed in the tissues. Our results using CAL 58 GBM cell line demonstrate a dose modification factor (DMF) of 1.19 when 100 ppm of boric acid are added to the growth medium. Thus for the particles, issued from neutron capture, a biological efficiency at least twice that of fast neutrons can be derived. These results, compared with historical data on fast neutron irradiation of glioblastoma, suggest that a therapeutic window may be obtained for GBM.

Boron Neutron Capture Therapy↗

[211At]methylene blue for targeted radiotherapy of human melanoma xenografts: dose fractionation in the treatment of cutaneous tumours.

3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] labelled with alpha-particle emitter astatine-211 (211At) selectively accumulates in melanoma cells due to an exceptionally high affinity of MTB to melanin, and proves to be a very effective agent in targeting radiotherapy for pigmented human melanoma grown in mice. This study aimed at a selection of the most advantageous [211At]MTB dose fractionation leading to irreversible regression of the treated lesions. Nude mice bearing subcutaneous human melanoma xenografts of either highly pigmented HX118 or poorly pigmented HX34 human melanoma were treated with [211At]MTB administered intravenously. The treatment was performed using three different schedules of [211At]MTB fractionation: a single large dose, five fractions delivered sequentially every 48 h and two to five fractions given with a mean frequency of one per week. The effectiveness of [211At]MTB treatment was assessed by determination of the growth rate of cutaneous tumours and length of time between tumour implantation and killing of moribund mice. [211At]MTB applied with a mean frequency of one fraction per week appeared to be the most efficient treatment for highly pigmented HX118 melanomas. Its effectiveness was dependent on [211At]MTB activity used per fraction and the size of the cutaneous tumours at the beginning of the treatment. A total dose of [211At]MTB seemed of less importance. An irreversible regression of the lesions was achieved. Poorly pigmented cutaneous melanoma xenografts were affected most significantly by [211At]MTB applied as five fractions given every 48 h. The treatment caused a temporary inhibition of tumour growth after which the lesions regained the control growth rate. These and previous results suggest that [211At]MTB could successfully control the growth of already formed lesions of pigmented melanoma, as well as prevent metastatic spread of the tumour, provided an appropriate fractionation régime of the radiolabelled compound is employed.

Animals↗

211At-methylene blue for targeted radiotherapy of disseminated melanoma: microscopic analysis of tumour versus normal tissue damage.

The present stage of our preclinical investigations of targeted radiotherapy for melanoma with 3,7-(dimethylamino)phenazathionium chloride [methylene blue (MTB)] labelled with astatine-211 (211At), an alpha-particle emitter, concerns toxicity of the treatment, as well as macro- and microscopic evaluation of its efficacy. Fragments of two human melanoma xenografts, pigmented HX118 and non-pigmented HX34 (used as a control), were implanted s.c. into nude mice subsequently treated with two doses of 211At-MTB injected i.v. Alterations in tumour growth rate were related to microscopic damage caused by 211At-MTB to the lesions, as determined by light microscopy using histopathological techniques. 211At-MTB-dependent growth inhibition of pigmented melanoma occurred either instantly or as a gradual reduction in the tumour growth rate. At a later stage, lesions that ceased to grow immediately consisted of quiescent, heavily pigmented tumour cells, as well as advanced fibrosis, and were extensively infiltrated by melanin-laden phagocytes. Large, unresorbed and often calcified necrotic deposits characterised the tumours responding gradually to the treatment. 211At-MTB remained non-toxic in normal organs. Only a relative number of small lymphocytes in the groin lymph nodes in a minority of animals was temporarily reduced, most often in conjunction with the treatment of pigmented tumours. The data demonstrated a high therapeutic effectiveness of 211At-MTB towards pigmented melanoma at the expense of negligible injury to normal tissues, and revealed that the macroscopic determination of tumour growth rate often underestimated an efficacy of the applied treatment.

Animals↗

Bone powder exposed to the action of 12C and 25Mg ion beams as investigated by electron paramagnetic resonance spectroscopy.

Bovine compact bone powder was irradiated with alpha-particles of 241Am, 12C6+ and 35Mg12+ ion beams, then examined by the e.p.r. spectroscopy. The stable e.p.r. signal found is of the same characteristic as that observed in gamma-irradiated bone (g perpendicular = 2.0017, g parallel = 1.9973, delta Hpp = 0.85 mT). Thus, the structure of radiation induced paramagnetic center in bone does not depend on the LET of radiation used. The radiolytic yields of the formation of stable paramagnetic centres in bone powder irradiated with gamma-rays are G gamma = 0.08 +/- 0.01 while with 12C6+ ion beams roughly about Gc = 0.02, respectively.

Animals↗

Environmental plutonium in humans.

Although the current world inventory of plutonium is overwhelmingly man-made, it is important to recognize that 244Pu was a primeval radioelement and that 239Pu is formed continuously by spontaneous fission of 238U; the atom ratio U:Pu being about 10(11):1. It has been calculated that the human body has always carried a base load of, perhaps 10(3)-10(5) atoms (< 0.2 amol) of natural plutonium. Since 1945, the release of 239Pu into the environment from atmospheric nuclear weapons testing has added to this base load a civilization-related load which, at approximately 300 fmol, is at least 5 orders of magnitude greater. Within the human body plutonium is deposited mainly in the liver and skeleton where it appears to be retained tenaciously with half-times of many years. Based on 1970-1980 levels, environmental plutonium may give rise to alpha-particle radiation doses of approximately 3-7 microSv/a in human bone and approximately 10-20 microSv/a in liver, doses which from our present understanding of the radio-and chemical toxicity of plutonium are far too small to cause any recognizable health effects.

Adult↗

Radon emanation measurements using silicon photodiode detectors.

Driven by the global concern about radon hazards, a wide variety of methods to measure radon and its decay products have been developed. Pin silicon photodiodes are increasingly applied in this field, their main advantages being high detection efficiency for alpha particles and low cost. In this paper, we present a system to determine the emanation factor for 222Rn from porous material based on a pin photodiode. This equipment is valid both for field and laboratory measurements, allowing to monitor the external emanation conditions by means of temperature, humidity and pressure sensors. To illustrate the capabilities of the system, we present two case studies of samples with high and low 226Ra content. The activity of this radionuclide in the samples had been previously determined by gamma-ray spectrometry.

Electrochemistry↗

Direct measurements of radon activity in water from various natural sources using nuclear track detectors.

Radon activities measured in several types of natural waters from the Santos region in Brazil are presented. Makrofol E polycarbonate plastic detector was used. The detector foils were exposed to radon emanating from the water samples for 30 days in a system of two tightly coupled cups, one of which contained the detector foil and the other hosted the analyzed water sample. After irradiation and chemical etching of the plastic foils, the tracks produced by the alpha particles emitted by radon and its progeny were counted with a system consisting of an optical microscope and a video camera. The measured radon radioactivities ranged from 0.95 to 36.00 Bq/l for ground waters, from 0.30 to 0.54 Bq/l for sea waters, from 0.39 to 0.47 Bq/l for tap waters, from 0.43 to 2.40 Bq/l for river waters, and amounted to 2.35 Bq/l for water from the Santos/São Vicente public water supply.

Brazil↗

Chemical composition identification using fast neutrons.

Measurements of characteristic gamma ray spectra resulting from A(n, n'gamma)A reactions induced by 14 eV neutrons on different bulk samples (graphite, water, melamin) were performed. Of particular importance are results of experiments with objects buried in the soil. It has been shown that samples of graphite can be identified when buried under 10 m of soil. NaI(Tl) and BaF(2) scintilators were used as gamma ray detectors. Background radiation was reduced by the associated alpha particle technique.

Journal Article↗

Aspects of sample preparation for the determination of actinoids in soil.

In the frame of the re-certification measurements of the IAEA-375 soil reference material the activity concentration of four actinoids (U, Th, Pu and Am) was determined. The method is based on microwave digestion or aqua regia leaching, separation by extraction chromatography and alpha-particle counting source preparation by co-precipitation or electro-deposition. This article describes some of the problems encountered during the validation of the sample preparation method and their solutions.

Actinoid Series Elements↗

Sequential isotopic determination of plutonium, thorium, americium, strontium and uranium in environmental and bioassay samples.

A procedure has been developed to provide sequential analysis of 238Pu, 230Th, 241Am, 238U, and 90Sr in environmental and bioassay samples. Tracers and/or carriers (242Pu, 243Am, 232U, and stable strontium) are added into the sample as chemical yield monitors, and then, plutonium, thorium, strontium, americium, and uranium are sequentially separated and purified by Dowex ion-exchange resin, EiChroM Sr-resin, EiChroM TRU-resin, and Chelate-100 resin, respectively. The radioactivities of 90Sr and the actinides are measured using the liquid scintillation counter and alpha-particle spectrometer, respectively. Acidified water, glass-fiber air filter, soil, synthetic urine and synthetic feces samples of US National Institute of Standard and Technology Radiochemical Intercomparison Program(NRIP) were analyzed to verify this method. All the analytical results of 238Pu, 230Th, 90Sr, 241Am and 238U meet the traceability limit per ANSI N42.22, and when appropriate, evaluation of radiobioassay measurement bias and precision per ANSI N13.30.

Chromatography, Ion Exchange↗

2003: a centennial of spinthariscope and scintillation counting.

In 1903 W. Crookes demonstrated in England his "spinthariscope" for the visual observation of individual scintillations caused by alpha particles impinging upon a ZnS screen. In contrast to the analogue methods of radiation measurements in that time the spinthariscope was a single-particle counter, being the precursor of scintillation counters since. In the same period F. Giesel, J. Elster and H. Geitel in Germany also found that scintillations from ZnS represent single particle events. This paper summarises the historical events relevant to the advent of scintillation counting.

Journal Article↗

A new internal target system for production of (211)At on the cyclotron U-120M.

The alpha emitter (211)At is a radionuclide with good potential for use in the therapy of smaller tumours and metastases. However, limited availability of this radionuclide hinders development of this application and the research of astatine chemistry in general. In this general context we have designed and tested a new internal target system. A thin bismuth layer (3-5 microm) was evaporated onto a light target backing (7.5 g) and irradiated at 0.5-1.5 degrees angles with 29.5 MeV alpha particles beam of intensity up to 30 microA. The backing was then released from the target holder and used directly for astatine separation via dry distillation. Astatine condensed on the Teflon capillary walls was then eluted into 150-250 microl of methanol. The saturation yield was found to be ca. 400 MBq/microA, and the radionuclidic purity of (211)At acceptable for medical applications (activity ratio (210)At/(211)At<10(-3) at EOB). The overall separation yield was 65-75%.

Journal Article↗