Comparison between 177Lu-iPSMA and 225Ac-iPSMA dosimetry at a cellular level in an animal bone metastasis model.

The recent use of prostate-specific membrane antigen as a biological target have improved the theragnostic approach to prostate and other types of cancer. Radiopharmaceuticals based on PSMA inhibitors radiolabeled with beta emitters as Lutetium-177 have demonstrated remarkable efficacy and safety, however, their clinical evaluation have also shown that therapeutic response of bone located metastases is poorer than that presented by soft tissue lesions. These observations conducted to the development and study at different levels of PSMA-targeting alpha-particle therapy exhibiting effective and promising antitumor activity. However, some aspects of the use of alpha emitters such as cellular dosimetry should be considered before applying them safely. The aim of the present work was to compare and calculate the absorbed dose of 177Lu-iPSMA and 225Ac-iPSMA using an animal bone metastasis model and experimental data obtained from cellular fractionation. The number of disintegrations and the dose factors for the theragnostic iPSMA pair, molecule that can be radiolabeled with 177Lu or 225Ac, were determined based on MIRD methodology, and used to calculate the absorbed dose to cell nucleus. A five times difference between 225Ac-iPSMA and 177Lu-iPSMA average dose rate to the tumor was calculated, being 2.3 ± 0.037 for the first and 0.5 ± 0.018 Gy for the second, both for each activity unit (MBq) administered.

Disequilibrium in the uranium and actinium series in oil scale samples.

We have investigated the disequilibrium of the uranium and actinium series and have found both 226Ra (90,200 ± 4300 Bq/kg) and 228Ra have activity concentrations orders of magnitude higher that 238U (1.83 ± 0.36 Bq/kg) and 232Th (7.0 ± 0.4) which are at the head of the decay series. As well the activity concentration of 210Pb (24,400 ± 1200 Bg/kg) was about 3.6 times less than 226Ra. Once an efficiency curve was constructed summing corrections for specific isotopes in the decay change also needed to be taken in consideration. Furthermore, self-attenuation of the photons especially the 46.5 keV belonging to 210Pb was calculated to be 78% since the scale had elevated elemental concentrations of high-Z elements such as barium and strontium.

Determination of (210)Pb and (226)Ra/(228)Ra in continental water using HIDEX 300SL LS-spectrometer with TDCR efficiency tracing and optimized α/ß-discrimination.

An analytical method for determination of (210)Pb, (226)Ra and (228)Ra is presented based on adsorption on 3M Empore RadDiscs, and measurement applying liquid scintillation spectrometry (LSC) after elution. The LSC measurement was performed with optimized α/ß-discrimination and isotope standardization using the triple to double coincidence ratio (TDCR). The consistency of measurement results between radioactive parent-daughter pairs (210)Pb/(210)Bi, (226)Ra/(222)Rn and (228)Ra/(228)Ac was checked in long-term counting experiments and the influence ofinterference of in-growing daughters from (226)Ra into the ß-spectrum of (228)Ra+(228)Ac was studied as well. Recommendations for optimized LSC (228)Ra measurement besides presence of (226)Ra are given.

A radiometric and petrographic approach to risk assessment at Alte Madonie Mounts region (Sicily, Italy).

The main goal of this work was to assess the radiological hazard at Alte Madonie Mounts region (north-central Sicily, Italy) in response to rumours of an increase in the incidence of cancer in this area. A correlation between the natural radionuclide contents and the petrographic features of the soil and rock samples was also evaluated. A total of 41 samples of selected soils and rocks were collected, powdered, dried and sealed in 'Marinelli' beakers for 20 d prior to measurement to ensure that a radioactive equilibrium between (226)Ra and (214)Bi had been reached. A gamma-ray spectrometer was used to quantify the radioactivity concentrations. To determine (238)U and (232)Th activities, the 609.3-keV line from (214)Bi in secular equilibrium with (226)Ra and the 911-keV line from (228)Ac, with which (232)Th can be assumed to be in equilibrium, were used, respectively. The gamma transition of 1461 keV was used to determine (40)K activity. The average values of the concentrations of (214)Bi, (228)Ac and (40)K were 30, 17 and 227 Bq kg(-1), respectively, whereas the greatest values were 134, 59 and 748 Bq kg(-1), respectively. A linear relationship was found between the activity values of (214)Bi, (228)Ac and (40)K. An exception was found for a group of samples in which the (214)Bi activities were much higher than expected. The chemical compositions and mineralogical features of the samples permitted the justification of these anomalies. The results of the primordial radionuclide contents are reassuring from a radiation protection point of view because the activities of the uranium and thorium series products and of the (40)K do not present a significant radiological hazard.

LAFARA: a new underground laboratory in the French Pyrénées for ultra low-level gamma-ray spectrometry.

We describe a new underground laboratory, namely LAFARA (for "LAboratoire de mesure des FAibles RAdioactivités"), that was recently created in the French Pyrénées. This laboratory is primarily designed to analyze environmental samples that display low radioactivity levels using gamma-ray spectrometry. Two high-purity germanium detectors were placed under 85 m of rock (ca. 215 m water equivalent) in the tunnel of Ferrières (Ariège, France). The background is thus reduced by a factor of ∼20 in comparison to above-ground laboratories. Both detectors are fully equipped so that the samples can be analyzed in an automatic mode without requiring permanent presence of a technician in the laboratory. Auto-samplers (twenty positions) and systems to fill liquid nitrogen automatically provide one month of autonomy to the spectrometers. The LAFARA facility allows us to develop new applications in the field of environmental sciences based on the use of natural radionuclides present at low levels in the environment. As an illustration, we present two of these applications: i) dating of marine sediments using the decay of (226)Ra in sedimentary barite (BaSO(4)), ii) determination of (227)Ac ((231)Pa) activities in marine sediment cores.

Natural and anthropogenic radionuclides in airborne particulate samples collected in Barcelona (Spain).

Results for naturally occurring (7)Be, (210)Pb, (40)K, (214)Bi, (214)Pb, (212)Pb, (228)Ac and (208)Tl and anthropogenic (137)Cs in airborne particulate matter in the Barcelona area during the period from January 2001 to December 2005 are presented and discussed. The (212)Pb and (208)Tl, (214)Bi and (214)Pb, (7)Be and (210)Pb radionuclide levels showed a significant correlation with each other, with correlation coefficients of 0.99, 0.78 and 0.69, respectively, suggesting similar origin/behaviour of these radionuclides in the air. Caessium-137 and Potassium-40 were transported to the air as resuspended particle from the soil. The (7)Be and (210)Pb concentrations showed similar seasonal variations, with a tendency for maximum concentrations during the summer months. An inverse relationship was observed between the (7)Be, (210)Pb, (40)K and (137)Cs concentrations and weekly rainfall, indicating washout of atmospheric aerosols carrying these radionuclides.

Radium-228 analysis of natural waters by Cherenkov counting of Actinium-228.

The activities of (228)Ra in natural waters were determined by the Cherenkov counting of the daughter nuclide (228)Ac. The radium was pre-concentrated on MnO(2) and the radium purified via ion exchange and, after a 2-day period of incubation to allow for secular equilibrium between the parent-daughter (228)Ra((228)Ac), the daughter nuclide (228)Ac was isolated by ion exchange according to the method of Nour et al. [2004. Radium-228 determination of natural waters via concentration on manganese dioxide and separation using Diphonix ion exchange resin. Appl. Radiat. Isot. 61, 1173-1178]. The Cherenkov photons produced by (228)Ac were counted directly without the addition of any scintillation reagents. The optimum Cherenkov counting window, sample volume, and vial type were determined experimentally to achieve optimum Cherenkov photon detection efficiency and lowest background count rates. An optimum detection efficiency of 10.9+/-0.1% was measured for (228)Ac by Cherenkov counting with a very low Cherenkov photon background of 0.317+/-0.013cpm. The addition of sodium salicylate into the sample counting vial at a concentration of 0.1g/mL yielded a more than 3-fold increase in the Cherenkov detection efficiency of (228)Ac to 38%. Tests of the Cherenkov counting technique were conducted with several water standards of known activity and the results obtained compared closely with a conventional liquid scintillation counting technique. The advantages and disadvantages of Cherenkov counting compared to liquid scintillation counting methods are discussed. Advantages include much lower Cherenkov background count rates and consequently lower minimal detectable activities for (228)Ra and no need for expensive environmentally unfriendly liquid scintillation cocktails. The disadvantages of the Cherenkov counting method include the need to measure (228)Ac Cherenkov photon detection efficiency and optimum Cherenkov counting volume, which are not at all required when liquid scintillation analysis is used.

Vertical distribution, migration rates, and model comparison of actinium in a semi-arid environment.

Vertical soil characterization and migration of radionuclides were investigated at four radioactively contaminated sites on Kirtland Air Force Base (KAFB), New Mexico to determine the vertical downward migration of radionuclides in a semi-arid environment. The surface soils (0-15 cm) were intentionally contaminated with Brazilian sludge (containing (232)Thorium and other radionuclides) approximately 40 years ago, in order to simulate the conditions resulting from a nuclear weapons accident. Site grading consisted of manually raking or machine disking the sludge. The majority of the radioactivity was found in the top 15 cm of soil, with retention ranging from 69 to 88%. Two models, a compartment diffusion model and leach rate model, were evaluated to determine their capabilities and limitations in predicting radionuclide behavior. The migration rates of actinium were calculated with the diffusion compartment and the leach rate models for all sites, and ranged from 0.009 to 0.1 cm/yr increasing with depth. The migration rates calculated with the leach rate models were similar to those using the diffusion compartment model and did not increase with depth (0.045-0.076, 0.0 cm/yr). The research found that the physical and chemical properties governing transport processes of water and solutes in soil provide a valid radionuclide transport model. The evaluation also showed that the physical model has fewer limitations and may be more applicable to this environment.

Natural radioactivity in phosphates, phosphogypsum and natural waters in Morocco.

The contents of natural radionuclides (uranium, actinium and thorium series) were measured in sedimentary phosphate rock samples using high-resolution gamma spectrometry. Data obtained for uranium content (ppm) were compared with the results obtained by a method based on the measurements using solid-state nuclear track detectors (SSNTD) in the same samples. The potential leaching of radionuclides from sedimentary phosphate rock during the industrial production of the phosphoric acid was studied. The process of leaching of the radioisotopes from phosphogypsum was discussed. A method for the direct alpha counting of 226Ra thin source, elaborated by the deposition of Ra from aqueous solutions on manganese oxides film deposited on polyvinyl support, have been developed and applied for the determination of 226Ra in natural water samples. The results show that only the water sample from the mine area reveals the presence of 226Ra at a level of about 0.2 Bq l-1.

Preparation of alpha-emitting 213Bi-labeled antibody constructs for clinical use.

UNLABELLED: Preclinical evaluation of alpha particle-emitting 213Bi-labeled antibody constructs have demonstrated the specificity and potency of these agents in a variety of cancer systems. The transition of a 213Bi-radiolabeled antibody from a preclinical construct to a clinical drug represented a difficult task that involved development of reliable and validated methods to provide multiple MBq quantities of a pure, immunoreactive agent that met pharmaceutical standards to treat patients. METHODS: The methods used for the preparation of (213Bi)CHX-A-diethylenetriamine pentaacetic acid (DTPA)-HuM195, an alpha particle-emitting anti-CD33 antibody construct for therapy of myeloid leukemias, is used as a specific example. This article describes methods for reagent purification, drug labeling, radioprotection and chromatographic purification. Quality of the drug is evaluated using radiochemical incorporation and purity assays with instant thin-layer chromatography (ITLC) and high-performance liquid chromatography (HPLC), determination of cell-based antibody total immunereactivity, small animal safety, pyrogen level, sterility and radionuclidic purity. RESULTS: Sixty-seven doses were prepared. Individual doses ranged from 148 to 814 MBq. Specific activities ranged from 329 to 766 MBq/mg. The radiolabeling efficiency (median +/- SD) of CHX-A-DTPA-HuM195 with 213Bi was 81% +/- 9% (n = 67) after 9 min. The construct was purified by size-exclusion chromatography and was found to be 99% +/- 2% pure (n = 67) by either ITLC or HPLC methods. The immunoreactivity of (213Bi)CHX-A-DTPA-HuM195 was 89% +/- 9% (n = 44) and was independent of the specific activity. The formulated pharmaceutical was found to contain < or =4 +/- 1 EU/mL pyrogens (n = 66); all samples examined were sterile. An 225Ac radionuclidic impurity was present at a level of 0.04 +/- 0.03 x 10(-6)/mL (n = 10) in a product volume of 7.4 +/- 0.5 mL (n = 67). Each of the 67 doses was injected intravenously into patients without complication as part of a phase I clinical trial. CONCLUSION: These data show that 213Bi-labeled antibody constructs can be prepared and administered safely to humans at a wide range of therapeutic levels.

Estimated absorbed dose in tissues and radiation effects in Japanese Thorotrast patients.

The absorbed dose in the liver, spleen and bone marrow of Thorotrast patients was estimated for 71 autopsy cases. 232Th amounts in tissues were determined from measurements of 228Ac gamma-rays and the activity ratio of 228Ac to 232Th. In calculating the absorbed dose, Kaul's data were used as values of the steady state activity ratio between 232Th and its daughters and the self-absorption of alpha-rays in Thorotrast aggregates. The autopsy cases in which the cumulative dose was estimated consisted of 45 cases of malignant hepatic tumor, 12 cases of liver cirrhosis, 7 cases of blood disease and 7 cases of other diseases. The estimated absorbed doses in the organs were presented and the relationship between the dose and radiation effects on organ tissues was discussed.