Biodistribution of 225Ra citrate in mice: retention of daughter radioisotopes in bone

Alpha-particle-emitting radionuclides have potential for therapy of localized disease due to their high linear energy transformation and short pathlengths. Radiometals that home naturally to bone can be exploited for this purpose, and ²²³Ra (t_1/2=11.4 days) recently has been studied for therapy of bone tumors in mice and rats. Actinium-225 (t_1/2=10 days) is also an attractive radioisotope for endoradiotherapy. In a single decay of a ²²⁵Ac nucleus and its subsequent decay daughters, over 27 MeV (90% of total energy) is released by sequential emission of four particles, ranging in energy from 5.7 to 8.4 MeV. Although Ac³⁺ does not home naturally to bone, its parent radioisotope ²²⁵Ra (β⁻, t_1/2=15 days) can be used as an in vivo source for ²²⁵Ac. Thus, injection of ²²⁵Ra takes advantage of the bone-homing properties of radium coupled with the significant amount of energy released from the ²²⁵Ac decay chain. Our data confirm that a large fraction of radium citrate injected intravenously into mice localizes rapidly in bone. Injected doses per gram (ID/g) for ²²⁵Ra range from 25% in skull to about 10% in sternum. Once deposited, the ²²⁵Ra remains in the bone with a biological half life of >40 days. Furthermore, >95% of the daughter radioisotope, ²²⁵Ac, is retained in the bone. However, a significant fraction of one of the daughter radioisotopes, ²¹³Bi, is found in kidney. The biodistribution data indicate that ²²⁵Ra injection should be a powerful agent for killing cells associated with bone; however, the toxicity of this radioisotope which is similar to that of other emitters limits the dose that can be tolerated.     

Preparation of carrier-free yttrium-90 for medical applications by solvent extraction chromatography

The separation of carrier-free ⁹⁰Y from fission product ⁹⁰Sr by solid supported solvent extraction chromatography was investigated using Teflon grain as solid support and a di-(2-ethylhexyl) phosphoric acid (D2EHPA) extraction agent as liquid phase. The optimum separation conditions are: (1) solid support using Dupont TF800 Teflon grains, (2) using 5% D2EHPA extraction agent as liquid phase, (3) setting the flow rate at 1 cm³/min, and (4) using a column diameter of 0.5 cm which was packed with 1 g treated Teflon. After loading ⁹⁰Sr/⁹⁰Y equilibrium solution, the loaded column was washed with 0.3 N hydrochloric acid to remove ⁹⁰Sr species; subsequently, 8 N hydrochloric acid was used as an eluent to obtain a ⁹⁰Y solution. Chemical yield was about 90%; radionuclide impurity of ⁹⁰Sr in the final product was <10⁻⁶%. Consequently, the preparation of 1 mCi of ⁹⁰Y was satisfactory for radiolabeling in medical applications. A radiotracer method using ⁸⁵Sr and ⁸⁸Y was also developed to investigate separation efficiency.     

Design and synthesis of Ac radioimmunopharmaceuticals

The alpha-particle-emitting radionuclides ²¹³Bi, ²¹¹At, ²²⁴Ra are under investigation for the treatment of leukemias, gliomas, and ankylosing spondylitis, respectively. ²¹³Bi and ²¹¹At were attached to monoclonal antibodies and used as targeted immunotherapeutic agents while unconjugated ²²⁴Ra chloride selectively seeks bone. ²²⁵Ac possesses favorable physical properties for radioimmunotherapy (10 d half-life and 4 net alpha particles), but has a history of unfavorable radiolabeling chemistry and poor metal-chelate stability. We selected functionalized derivatives of DOTA as the most promising to pursue from out of a group of potential ²²⁵Ac chelate compounds. A two-step synthetic process employing either MeO–DOTA–NCS or 2B–DOTA–NCS as the chelating moiety was developed to attach ²²⁵Ac to monoclonal antibodies. This method was tested using several different IgG systems. The chelation reaction yield in the first step was 93±8% radiochemically pure (n=26). The second step yielded ²²⁵Ac–DOTA–IgG constructs that were 95±5% radiochemically pure (n=27) and the mean percent immunoreactivity ranged from 25% to 81%, depending on the antibody used. This process has yielded several potential novel targeted ²²⁵Ac-labeled immunotherapeutic agents that may now be evaluated in appropriate model systems and ultimately in humans.     

Preparation of in-house reference soil sample containing high levels of naturally occurring radioactive materials from the oil industry

An in-house reference soil sample containing high levels of naturally occurring radioactive materials collected from contaminated areas in the Syrian oilfields has been prepared as a part of the quality assurance program in AECS. Homogeneity of the sample has been examined using three methods, viz. particle size distribution of the sample matrix, total alpha/beta counting and gamma spectrometry. In conjunction with Dixon and Grubb tests as statistical tools, ten random samples from the original sample were used for this investigation. Reference values for the three radium isotopes (²²⁴Ra, ²²⁶Ra, ²²⁸Ra) were determined using gamma spectrometry equipped with HPGe detectors having high relative efficiencies of 80%, while the reference value of ²¹⁰Pb in the sample was determined using radiochemical separation and counting of its daughter ²¹⁰Po by alpha spectrometry. ANOVA analysis was used to estimate the uncertainties due to measurement and inhomogeneity of the sample; uncertainty due to inhomogeneity was found to be around 2.6 times the measurement uncertainty.     

Gamma spectroscopic assay of soil samples from waste dump sites in Port Harcourt, Nigeria

A lead shielded 7.6 cm×7.6 cm NaI (Tl) detector and a Canberra Multichannel Analyzer were employed for a gamma spectrometric assay of 100 soil samples from refuse dump sites in Port Harcourt city and environs. The massic activities of ⁴⁰K, ²²⁶Ra and ²²⁸Ra were determined and found to correspond to natural levels of some 10 Bq/kg. No gamma-emitting anthropogenic radionuclides were detected. The mean radium equivalent is 44.2 Bq/kg giving a dose rate of 24.6 μSv/year.     

New ion exchange materials for use in a Sr/Rb generator

⁸²Rb is a short-lived positron-emitting isotope (T_1/2=75 s) that is increasingly being used in positron emission tomography for the evaluation of myocardial perfusion. The short half-life of ⁸²Rb results in rapid decay of the administered radioactivity allowing repeat scans to be performed after a relatively short time interval. The ⁸²Rb is available from a ⁸²Sr/⁸²Rb generator in which the ⁸²Sr parent is immobilized on an ion exchange column and ⁸²Rb eluted when required. Consequently, suitable ion exchangers for use in a generator must have a very high affinity for strontium and a negligible affinity for rubidium, allowing the pure ⁸²Rb to be safely and efficiently eluted in high yields. This study evaluated a number of strontium-selective ion exchange materials using batch experiments and identified sodium nonatitanate as the best material for use in a ⁸²Sr/⁸²Rb generator.     

An inter-laboratory comparison of low-level measurements in ground-level aerosol monitoring

After the nuclear reactor accident of Chernobyl, the “Integrated Measurement and Information System (IMIS) for Monitoring the Environmental Radioactivity and Detecting Emissions from Nuclear Plants was implemented in Germany. IMIS is a nationwide comprehensive measuring system which permanently monitors the radioactivity in all important environment media in the whole federal territory. At approximately 40 sites, the activity concentration of radioactive substances is measured in air and precipitations. At least 14 of them are responsible for trace monitoring of radionuclides in the air. The legal bases of IMIS prescribe regular inter-laboratory comparison analyses in cooperation with the Physikalisch-Technische Bundesanstalt (PTB), with the use of reference materials prepared by the Federal Coordinating Laboratories. In order to fulfil this requirement in the field of trace survey measurements in ground-level air, the Federal Office for Radiation Protection (“Bundesamt für Strahlenschutz”, BfS) and the PTB have conducted a comparison with real, dust-loaded reference filters in 2005. The comparison was organized within the framework of a cooperation of trace survey stations from Austria, Germany and Switzerland. The paper describes the preparation of the real, dust-loaded reference filters, the procedure for spiking the filters with the activity standard solution containing ²²Na, ⁸⁸Y, ⁸⁹Sr, ⁹⁰Sr, ¹²⁵Sb, ¹³³Ba, ¹³⁴Cs, and ²⁴¹Am. Some results are discussed and conclusions are given.     

Distribution of radiocesium and natural gamma emitters in pine needles in coniferious forest sites of Izmir

Using a high-resolution gamma-spectrometer system, the activity concentrations of ⁷Be, ¹³⁷Cs, ⁴⁰K and ²²⁶Ra were determined in the pine needles. Activity concentrations of the concerned radionuclides in the needle samples were as follows: ⁷Be, 24.6±2.40 to 210±7.21 Bq kg⁻¹, ⁴⁰K, 23.5±12.4 to 287±15.6 Bq kg⁻¹, ²²⁶Ra, 0.44±0.12 to 12.3±2.18 Bq kg⁻¹, and ¹³⁷Cs, 0.61±0.30 to 2.29±0.38 Bq kg⁻¹. It is found that the frequency distributions obtained for ⁷Be and ¹³⁷Cs can be fitted to a normal distribution, and for ⁴⁰K and ²²⁶Ra can be fitted to a log-normal distribution.     

On the use of mercury as a means of locating background sources in ultra low-background HPGe-detector systems

In low-level gamma-ray spectrometry, it is common to measure large samples in order to obtain low detection limits for the massic activity (in mBq/kg). These samples have significant shielding effects. In order to study whether the background sources in three ultra low-background HPGe detectors were located in the detector or in the shield, Marinelli beakers filled with hyperpure mercury were measured. Although the measurements were hampered by the presence of cosmogenically produced ¹⁹⁴Hg, information regarding the major background location of ⁴⁰K, ⁶⁰Co, ¹³⁷Cs, ²¹⁰Pb, ²²⁶Ra, ²²⁸Ra and ²²⁸Th could be obtained.     

Manufacture of strontium-82/rubidium-82 generators and quality control of rubidium-82 chloride for myocardial perfusion imaging in patients using positron emission tomography

We describe a protocol to manufacture ⁸²Sr/⁸²Rb generators and ⁸²RbCl for myocardial imaging with PET. The generators are manufactured in 3 stages: (1) preparation of a tin oxide column, (2) leak test of the generator column and (3) loading of the generator with ⁸²Sr. The generators produced sterile and non-pyrogenic ⁸²RbCl for i.v. injection. No significant ⁸²Sr/⁸⁵Sr breakthroughs were observed after elution with 20 l of saline. The automated system delivered human doses of ⁸²RbCl accurately.     

Reusability of plastic scintillators used in beta emitter activity determination

The use of plastic scintillation in the measurement of beta emitter activity is a suitable alternative to classical detection techniques in spite of the high cost and potential memory effects. Reuse of the plastic scintillator beads after a cleanup procedure would overcome both drawbacks.

In the present paper, we tested several cleaning solutions (water, HCl 0.1 M, commercial soap, EDTA 0.01 M pH=3, citric acid 0.1 M pH=3). The recommended procedure consists of the immersion of the beads in three consecutive citric acid baths for 24 h. If this protocol is followed, plastic beads contaminated with ⁹⁰Sr/⁹⁰Y, ¹⁴C, and ³H recover their initial condition, and can be used in successive determinations.     

Cherenkov counting of yttrium-90 in the dry state; correlations with phosphorus-32 Cherenkov counting data

We present data that illustrate some advantages of Cherenkov counting for the radioassay of ⁹⁰Y in the dry state and provide recommendations concerning sample counting geometry. Slightly higher detection efficiencies and figures-of-merit were obtained when counting ⁹⁰Y in the dry state in polyethylene plastic counting vials compared to the counting of ⁹⁰Y in 20 ml of water in borosilicate glass vials. The effects of polyethylene plastic counting vials and sample counting geometry are compared to similar data obtained in the Cherenkov counting of ³²P. Data are presented to interpret the effects of polyethylene plastic and borosilicate glass on Cherenkov counting efficiency and background counts. Applications of the Cherenkov counting of ⁹⁰Y and ³²P in the dry state in the biological and radiopharmaceutical sciences are foreseen as well as applications in the analysis of ⁹⁰Sr(⁹⁰Y) and ³²P in health physics and environmental monitoring.     

[Dy]Dy/Ho hydroxide macroaggregates: an in vivo generator system for radiation synovectomy

Radiation synovectomy is an effective treatment in patients suffering from inflammatory-rheumatoid and degenerative joint diseases. The aim of this work was to examine the feasibility of preparing dysprosium-166 (¹⁶⁶Dy)/holmium-166(¹⁶⁶Ho) hydroxide macroaggregates ([¹⁶⁶Dy]Dy/¹⁶⁶Ho-HM) as an in vivo generator for radiation synovectomy evaluating whether the stability of ¹⁶⁶Dy-HM and ¹⁶⁶Ho-HM complexes is maintained when the daughter ¹⁶⁶Ho is formed. The Monte Carlo (MCNP4B) theoretical depth dose profile for the in vivo [¹⁶⁶Dy]Dy/¹⁶⁶Ho generator system in a joint model was calculated and compared with that produced by ⁹⁰Y, ¹⁵³Sm and ¹⁶⁶Ho. ¹⁶⁶Dy was obtained by neutron irradiation of enriched ¹⁶⁴Dy₂O₃ in a Triga Mark III reactor. Macroaggregates were prepared by reaction of [¹⁶⁶Dy]DyCl₃ with 0.5 M NaOH in an ultrasonic bath. [¹⁶⁶Dy]Dy/¹⁶⁶Ho-HM was obtained with radiochemical purity >99.5% and with the majority of particles in the 2–5 μm range. In vitro studies demonstrated that the radio-macroaggregates are stable in saline solution and human serum without a significant change in the particle size over 14 d, suggesting that no translocation of the daughter nucleus occurs subsequent to β⁻ decay of ¹⁶⁶Dy. Biological studies in normal rats demonstrated high retention in the knee joint even 7 d after [¹⁶⁶Dy]Dy/¹⁶⁶Ho-HM administration. The Monte Carlo (MCNP4B) theoretical depth dose profiles in a joint model, showed that the in vivo [¹⁶⁶Dy]Dy/¹⁶⁶Ho generator system would produce 25% and 50% less radiation dose to the articular cartilage and bone surface, respectively, than that produced by ⁹⁰Y or pure ¹⁶⁶Ho in a treatment with the same therapeutic dose to the synovium surface. Despite that ¹⁵³Sm showed the best depth dose profile sparing doses to healthy tissues, the use of ¹⁶⁶Dy could provide the advantage of being applied in patients that cannot be reached within a few hours from a nuclear reactor and to produce less radiation exposure to the medical personnel during the radiopharmaceutical administration.     

Separation of carrier-free Re produced in O-irradiated thulium target

Heavy ion activation of natural Tm₂O₃ with 90 MeV ¹⁶O beam results in the formation of carrier-free short-lived ¹⁸¹Ir and ¹⁸¹Os which ultimately decay out to ¹⁸¹Re in the matrix. The liquid cation exchanger, HDEHP, has effectively been utilized as an extractant for quantitative separation of bulk thulium target matrix from carrier-free rhenium radionuclide.     

Radioactivity in some gas-flow lantern mantles produced by different manufacturers

Groups of gas-flow lantern mantles of different manufacturers were subjected to radiometric investigation to evaluate the radiological hazards arising from their usage. Interest was given to the long-lived radionuclides found, which were the -emitting nuclides of thorium and ²²⁸Ra. Thorium isotopes were analyzed by -spectrometry whereas ²²⁸Ra was analyzed by γ-spectrometry. The results show that mantles from different manufacturers contain mainly natural thorium with levels that fluctuate over a very wide range, from 350 to 4560 Bq/mantle. For the same manufacturer, thorium levels vary strongly in mantles of different batches and even from the same batch. On burning the mantle, a 10–20% reduction in the thorium activity takes place in the first few minutes. The mantle containers were almost free from significant thorium contamination. Results are given and discussed in detail.     

The Br(p,x)Se nuclear processes: a convenient route for the production of radioselenium tracers relevant to amino acid labelling

A possible route for the production of no-carrier-added (n.c.a.) ⁷³Se (T_1/2=7.1 h) and ⁷⁵Se (120 d) is introduced. -2-Amino-4-([⁷³Se]methyl-seleno) butanoic acid ( -[⁷³Se]selenomethionine) with an overall radiochemical yield of >40% could be prepared via a 3-step polymer-supported synthesis after successful separation of ⁷³Se from KBr targets. Excitation functions for the ^natBr(p,x) ^72,73,75Se processes were measured from threshold up to 100 MeV utilizing pellets of pressed KBr. Targets were irradiated at the NAC cyclotron with proton beams having primary energies of 40.4, 66.8 and 100.9 MeV. The calculated ⁷³Se yield (EOB) for 1 h irradiation in 1 μA of beam at the optimum proton energy range of 62→42 MeV is 81.4 MBq (2.2 mCi), and the calculated ⁷⁵Se yield (EOB) for the overall range 62 MeV→threshold for the same irradiation conditions is 0.97 MBq (0.026 mCi).     

Direct gamma-spectrometric measurement of the Ra 186.2 keV line for detecting U/Ra disequilibrium in determining the environmental dose rate for the luminescence dating of sediments

In the age determination of sediments according to the luminescence method, it is important to know whether there was secular equilibrium in the Th and U decay series during accumulation of the environmental radiation dose in geological times. This can be investigated via gamma-ray spectrometry, whereby—in the ²³⁸U series—²¹⁴Pb and ²¹⁴Bi are considered as the indicators for ²²⁶Ra-mobility, and ²¹⁰Pb as the indicator for ²²⁶Rn-emanation. In the present work, the direct measurement of ²²⁶Ra—which can give extra information on the interpretation of the radioactive equilibrium—is investigated as to its precision and accuracy. Since there is a serious spectral interference on its 186.2 keV gamma-line (by ²³⁵U at 185.7 keV), various correction procedures were outlined and their performance was checked via the analysis of (certified) reference materials, leading to the recommendation of a “method of choice”.     

Radioactivity determination of individual radionuclides in a mixture by liquid scintillation spectra deconvolution

A spectrum deconvolution method has been applied to logarithmic liquid scintillation spectra containing more than one radionuclide, to determine the activity of the individual components. The shape of the sample spectrum has been used for resolving the various components in the sample by fitting the reference spectrum of each component to the measured composite spectrum. The procedure has been applied to environmental samples containing ⁹⁰Sr, ⁹⁰Y and ⁸⁵Sr, added as a tracer for the chemical recovery determination. Comparisons are made with results obtained using a modified window-based method and results obtained by measuring the ⁸⁵Sr activity by gamma-ray spectrometry and subtracting its contribution to the LS count rate. It is demonstrated that this treatment of the beta-particle spectra represents a rapid and reliable method of determining these radionuclides in a mixture, even at low activity levels.     

Calibration of a radionuclide calibrator system as a Bulgarian standard for activity

A commercially available radionuclide calibrator of the type Curiementor 3 (PTW, Freiburg, Germany) was calibrated using activity standard solutions, from the Physikalisch-Technische Bundesanstalt (PTB), of a number of photon-emitting radionuclides, in particular those used in nuclear medicine: ¹⁸F, ⁵¹Cr, ⁶⁷Ga, ^99mTc, ¹¹¹In, ¹²³I, ¹²⁵I, ¹³¹I, ¹⁸⁶Re, ²⁰¹Tl, and for beta-emitting nuclides: ³²P, ⁸⁹Sr, ⁹⁰Y, ²⁰⁴Tl. An energy-dependent efficiency curve was established to calculate efficiencies for photon-emitting radionuclides. The differences between experimental and calculated radionuclide efficiencies of the measuring system are of the order of a few percent. The performance of the system was checked for instrument stability, using a long-lived ¹³⁷Cs source, and for linearity using the decay of a ^99mTc source. The calibration measurements were carried out with 2 g of solution in standard PTB-type glass ampoules. The dependence of efficiency with varying solution mass and changing ampoule geometry is studied for some of the radionuclides. For example, geometry correction factors are determined for various solution volumes or ampoules with different wall thickness. The measuring system will enable the National Centre of Metrology (NCM) of Bulgaria to provide calibration services for activity measurements, which are traceable to PTB standards, and to organize national comparisons in order to improve the quality of measurements for nuclear medicine in Bulgarian hospitals. Furthermore, it should enable NCM to declare Calibration and Measurement Capabilities (CMCs) and to submit radioactive solutions to the International Reference System (SIR) at the BIPM in order to compare the results with Key Comparison Reference Values (KCRVs).     

Preliminary results on the production of short-lived radioisotopes with a Plasma Focus device

An experimental campaign was conducted to assess the feasibility of short-lived radioisotope (SLR) production within the pulsed discharges of a Plasma Focus (PF) device. This so-called “endogenous production” technique rests on the exploitation of nuclear reactions for the creation of SLR directly within the plasma, rather than on irradiating an external target. Until now only one research group has published data relevant to PF endogenous production of SLR, and the data seem to confirm that the PF has the capability to breed SLR. The campaign demonstrated production of ¹⁵O, ¹⁷F and ¹³N from the ¹⁴N(d,n)¹⁵O, ¹²C(d,n)¹³N and ¹⁶O(d,n)¹⁷F reactions. A 7 kJ, 17 kV Mather-type PF was operated with natural nitrogen, oxygen, CO₂ and deuterium in the vacuum chamber. Results to date confirm that, with a PF of this type, up to 1 μCi of SLRs per discharge can be obtained.