A suitable time point for quantifying the radiochemical purity of 225Ac-labeled radiopharmaceuticals

Background As 225Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and QC testing. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an 225Ac-labeled radiopharmaceutical can be accurately quantified. Results Six ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP for any pre-equilibrium measurement taken at an early time point. The 585 TLC measurements span RCP values of 1.8–99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. A measurement of RCP > 90% at 2 h predicts a true RCP > 97% and guarantees that RCP will exceed 90% after secular equilibrium is reached. These findings were independently validated using NaI(Tl) scintillation counting and high resolution gamma spectroscopy on a smaller set of samples with 10% ≤ RCP ≤ 100%. Conclusions RCP of 225Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC using various methods of quantifying particle emissions. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.

Natural Radionuclide Concentrations and Associated Doses Around Three Dumpsites in Lagos, Nigeria

Monitoring of environmental radiation helps to ascertain healthy vicinity which is a catalyst to the economic development of the area. Activity concentration of naturally occurring radionuclides in three (3) dumpsites in Lagos State, Olusosun Landfill, Ojota, Ilupeju dumpsite and, Gbagada dumpsite Lagos state, Nigeria were investigated using gamma-ray spectroscopy to obtain the level of radioactive exposure hazards experienced by people living in these vicinities. A total of thirty soil samples were randomly collected into a polythene bag. They were oven-dried at 110°C, pulverized, and sieved. Quantities of the samples (400 g) were sealed in cylindrical sample holders and kept for about 28 days to attain secular equilibrium between 226Ra and its decay products before analysis using gamma-ray spectrometry. The mean activity concentration obtained for 40K, 238U, and 234Th at, Ilupeju, Gbagada, and Ojota were 339.23±33.66, 11.83±19.174, 11.95±22.752 Bq/kg, 337.56 ± 36.22, 11.49±22.14, 11.54 ± 19.33 Bq/kg and 334.87±32.44, 11.42±22.39, 11.56±18.52 Bq/kg respectively. The mean absorbed dose nGy/h, annual effective dose mSv/y were calculated and their results were found to be below the global values. The results indicate that the radiation level within the dumpsites poses no significant health risk to the people living close to the dumpsites.

Rapid Extraction Chemistry Using a Single Column for 230Th/U Dating of Quaternary Hydrothermal Sulfides

230Th/U dating can provide high-precision age constraints on Quaternary hydrothermal sulfides. However, low content of U and Th often involves extraction chemistry for the separation and enrichment of U and Th, but these chemical processes are very complex. We developed a simplified procedure consisting of total sample dissolution and single-column extraction chemistry, which can reduce the time and improve the accuracy of the dating. Concentrated HCl-HF followed by HNO3 was added to ensure complete dissolution. A single column filled with 0.4 mL of AG 1-X8 anion resin was used, then 8 M HNO3, 8 M HCl and 0.1 M HNO3 were used to elute most of the matrix metals, Th and U. This process provided more than 95% recoveries for U and Th, and negligible blanks. Meanwhile, Pb and Bi interferences were tested and showed no effect on the U and Th isotope ratio. The 230Th/238U activity of the Geological Survey of Japan geochemical reference material JZn-1 in secular equilibrium was determined and showed a radioactive equilibrium (1.00 ± 0.01, n = 5, all errors 2σ) and an in-house standard QS-1 was consistent to 0.0078 ± 0.0001 (n = 8, ±2σ) with an average age of 705 ± 10 yrs BP (n = 8, ±2σ). The technique greatly shortens the sample preparation time and allows more concise and effective analysis of U-Th isotopes. It is ideally suited for the high-precision 230Th/U dating of Quaternary submarine hydrothermal sulfides and sulfides from other settings.

Numerical Solution of Radioactive Core Decay Activity Rate of Actinium Series Using Matrix Algebra Method

The Actinium 235 series is one of the radioactive series which is widely used as a raw material for reactors and nuclear activities. The existence of this series is found in several countries such as West USA, Canada, Australia, South Africa, Russia, and Zaire. The purpose of this study was to determine the activity value and the number of radioactive nucleus decay atoms on the actinium 235 rendered in a very long decay time of 4.3 x 109 years. The decay count in this study uses an algebraic matrix method to simplify the chain decay solution, which generally uses the concept of differential equations. The solution using this method can be computationally simulated using the Matlab program. This study indicates that the value of the decay activity experienced by each element in this series is the same, which is equal to 2,636 x 1011 Bq. This condition causes the actinium 235 series to experience secular equilibrium because the half-life of the parent nuclide is greater than the nuclide derivatives. The decay activity of the radioactive nucleus under the actinium 235 series is strongly influenced by the half-life of the nuclides, the decay constants, and the number of atoms after decay

A Consensus Time for Performing Quality Control of 225Ac-Labeled Radiopharmaceuticals

Background: As 225Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and analysis. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an 225Ac-labeled radiopharmaceutical can be accurately calculated. Results: Six ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP using pre-equilibrium measurements at early time points. The 585 TLC measurements span RCP values of 1.8% to 99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. At 2 h the mean average error is < 3%. A measurement of RCP > 90% at this time point predicts a true RCP > 97%. These findings were independently validated using NaI(Tl) scintillation counting and high resolution gamma spectroscopy on a smaller set of samples with 10% ≤ RCP ≤ 100%. Conclusions: RCP of 225Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC using various methods of quantifying particle emissions. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.

Water transfer to the deep mantle through hydrous, Al-rich silicates in subduction zones

Constraining deep-water recycling along subduction zones is a first-order problem to understand how Earth has maintained a hydrosphere over billions of years that created conditions for a habitable planet. The pressure-temperature stability of hydrous phases in conjunction with slab geotherms determines how much H2O leaves the slab or is transported to the deep mantle. Chlorite-rich, metasomatic rocks that form at the slab-mantle interface at 50–100 km depth represent an unaccounted, H2O-rich reservoir in subduction processes. Through a series of high-pressure experiments, we investigated the fate of such chlorite-rich rocks at the most critical conditions for subduction water recycling (5–6.2 GPa, 620–800 °C) using two different natural ultramafic compositions. Up to 5.7 GPa, 740 °C, chlorite breaks down to an anhydrous peridotite assemblage, and H2O is released. However, at higher pressures and lower temperatures, a hydrous Al-rich silicate (11.5 Å phase) is an important carrier to enable water transfer to the deep mantle for cold subduction zones. Based on the new phase diagrams, it is suggested that the deep-water cycle might not be in secular equilibrium.

Quantification of excess 231Pa in late Quaternary igneous baddeleyite

Initial excess protactinium (231Pa) is a frequently suspected source of discordance in baddeleyite (ZrO2) geochronology, which limits accurate U/Pb dating, but such excesses have never been directly demonstrated. In this study, Pa incorporation in late Holocene baddeleyite from Somma-Vesuvius (Campanian Volcanic Province, central Italy) and Laacher See (East Eifel Volcanic Field, western Germany) was quantified by U-Th-Pa measurements using a large-geometry ion microprobe. Baddeleyite crystals isolated from subvolcanic syenites have average U concentrations of ~200 ppm and are largely stoichiometric with minor abundances of Nb, Hf, Ti, and Fe up to a few weight percent. Measured (231Pa)/(235U) activity ratios are significantly above the secular equilibrium value of unity and range from 3.4(8) to 14.9(2.6) in Vesuvius baddeleyite and from 3.6(9) to 8.9(1.4) in Laacher See baddeleyite (values within parentheses represent uncertainties in the last significant figures reported as 1σ throughout the text). Crystallization ages of 5.12(56) ka (Vesuvius; MSWD = 0.96, n = 12) and 15.6(2.0) ka (Laacher See; MSWD = 0.91, n = 10) were obtained from (230Th)/(238U) disequilibria for the same crystals, which are close to the respective eruption ages. Applying a corresponding age correction indicates average initial (231Pa)/(235U)0 of 8.8(1.0) (Vesuvius) and 7.9(5) (Laacher See). For reasonable melt activities, model baddeleyite-melt distribution coefficients of DPa/DU = 5.8(2) and 4.1(2) are obtained for Vesuvius and Laacher See, respectively. Speciation-dependent (Pa4+ vs. Pa5+) partitioning coefficients (D values) from crystal lattice strain models for tetra- and pentavalent proxy ions significantly exceed DPa/DU inferred from direct analysis of 231Pa for Pa5+. This is consistent with predominantly reduced Pa4+ in the melt, for which D values similar to U4+ are expected. Contrary to common assumptions, baddeleyite-crystallizing melts from Vesuvius and Laacher See appear to be dominated by Pa4+ rather than Pa5+. An initial disequilibrium correction for baddeleyite geochronology using DPa/DU = 5 ± 1 is recommended for oxidized phonolitic melt compositions.

A Consensus Time for Performing Quality Control of 225Ac-Labeled Radiopharmaceuticals

Background: As 225Ac-labeled radiopharmaceuticals continue to show promise as targeted alpha therapeutics, there is a growing need to standardize quality control (QC) testing procedures. The determination of radiochemical purity (RCP) is an essential QC test. A significant obstacle to RCP testing is the disruption of the secular equilibrium between actinium-225 and its daughter radionuclides during labeling and analysis. In order to accelerate translation of actinium-225 targeted alpha therapy, we aimed to determine the earliest time point at which the RCP of an 225Ac-labeled radiopharmaceutical can be accurately calculated.Results: Six ligands were conjugated to macrocyclic metal chelators and labeled with actinium-225 under conditions designed to generate diverse incorporation yields. RCP was determined by radio thin layer chromatography (radioTLC) followed by exposure of the TLC plate on a phosphor screen either 0.5, 2, 3.5, 5, 6.5, or 26 h after the plate was developed. The dataset was used to create models for predicting the true RCP using pre-equilibrium measurements at early time points. The 585 TLC measurements span RCP values of 1.8% to 99.5%. The statistical model created from these data predicted an independent data set with high accuracy. Predictions made at 0.5 h are more uncertain than predictions made at later time points. This is primarily due to the decay of bismuth-213. At 2 h the mean average error is < 3%. A measurement of RCP > 90% at this time point predicts a true RCP > 97%.Conclusions: RCP of 225Ac-labeled radiopharmaceuticals can be quantified with acceptable accuracy at least 2 h after radioTLC. This time point best balances the need to accurately quantify RCP with the need to safely release the batch as quickly as possible.

Towards a revision of 234U and 230Th decay constants

&lt;p&gt;The quality of uranium-series ages depends on the accuracy and precision at which the decay constants of 234U, 230Th and 238U are determined. Here, we present intermediate results for a revision of the decay constants of 234U and 230Th. Therefore, we examined a selection of different materials in secular equilibrium using isotope dilution multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). New approaches of our study in particular concern the characterization of routines for measuring all isotopes on Faraday cups, i. e. low abundance isotopes on cups with 10^13 Ohm amplifiers, and a different selection of materials in comparison to previous studies.&amp;#160; &amp;#955;_234 could be determined so far at a precision of 24 &amp;#949; and agrees with the latest literature value of Cheng et al. (2013) within its error margins.&lt;/p&gt;

The use of self-induced X-ray fluorescence in gamma-ray spectroscopy of uranium ore samples

Gamma logging for uranium exploration are currently based on total counting with Geiger Müller gas detectors or NaI (TI) scintillators. However, the total count rate interpretation in terms of uranium concentration may be impaired in case of roll fronts, when the radioactive equilibrium of the natural 238U radioactive chain is modified by differential leaching of uranium and its daughter radioisotopes of thorium, radium, radon, etc. Indeed, in case of secular equilibrium, more than 95 % of gamma rays emitted by uranium ores come from 214Pb and 214Bi isotopes, which are in the back-end of 238U chain. Consequently, these last might produce an intense gamma signal even when uranium is not present, or with a much smaller activity, in the ore. Therefore, gamma spectroscopy measurements of core samples are performed in surface with high-resolution hyper-pure germanium HPGe detectors to directly characterize uranium activity from the 1001 keV gamma ray of 234mPa, which is in the beginning of 238U chain. However, due to the low intensity of this gamma ray, i.e. 0.84 %, acquisitions of several hours are needed. In view to characterize uranium concentration within a few minutes, we propose here a method using both the 92 keV gamma ray of 234Th and the 98.4 keV uranium X-ray. This last is due to uranium self-induced fluorescence caused by gamma radiations of 214Pb and 214Bi, which create a significant Compton scattering continuum acting as a fluorescence source and resulting in the emission of uranium fluorescence X-rays. The comparison of the uranium activity obtained with the 92 keV and 98.4 keV lines allows detecting a uranium heterogeneity in the ore. Indeed, in case of uranium nugget, the 92 keV line leads to underestimated uranium concentration due to gamma self-absorption, but on the contrary the 98.4 keV line leads to an overestimation because of increased fluorescence. In order to test this new approach, several tens of uranium ore samples have been measured with a handheld HPGe FALCON 5000 detector.