IAEA Activities on 67Cu, 186Re, 47Sc Theranostic Radionuclides and Radiopharmaceuticals.

Despite interesting properties, the use of 67Cu, 186Re and 47Sc theranostic radionuclides in preclinical studies and clinical trials is curtailed by their limited availability due to a lack of widely established production methods. An IAEA Coordinated Research Project (CRP) was initiated to identify important technical issues related to the production and quality control of these emerging radionuclides and related radiopharmaceuticals, based on the request from IAEA Member States. The international team worked on targetry, separation, quality control and radiopharmaceutical aspects of the radionuclides obtained from research reactors and cyclotrons leading to preparation of a standard recommendations for all Member States. The CRP was initiated in 2016 with fourteen participants from thirteen Member States from four continents. Extraordinary results on the production, quality control and preclinical evaluation of selected radionuclides were reported in this project that was finalized in 2020. The outcomes, outputs and results of this project achieved by participating Member States are described in this minireview.

Biosynthetic new composite material containing CuO nanoparticles produced by Aspergillus terreus for 47Sc separation of cancer theranostics application from irradiated Ca target.

Copper oxide nanoparticles (CuO NPs) are needed in various fields, especially in the biomedical field. CuO NPs was obtained from Aspergillus terreus filtrate. CuO NPs structure was confirmed by UV-Vis spectrophotometry, as well as Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). XRD offers the nanoparticles purity of CuO biosynthesis. CuO NPs are spherical when examined with TEM. The average size of CuO NPs from TEM was 15.75 ± 3.95 nm. New composite of P (AA-AN)-NPs CuO was synthesized by biotechnology and the induced γ-radiation. The distribution coefficient value (Kd) of 47Sc(III) as well as 47Ca(II) ions for the synthetic new composite was determined by batch technique. Radiochemical separation of 47Sc(III) from irradiated calcium target was studied using chromatographic column packed with the new composite material. The recovery yield of 78 ± 1.2% for 47Sc(III) was obtained using 1 M HCl. The quality control tests (chemical, radionuclide and radiochemical purities) of the eluted 47Sc confirmed that it's adequate for nuclear medicine applications.

Primary standardization and determination of gamma ray emission intensities of Ho-166.

The procedure followed by the Nuclear Metrology Laboratory (LMN) at the IPEN-CNEN/SP, in São Paulo, for the primary standardization of 166Ho is described. The activity of 166Ho was determined by the efficiency extrapolation technique applied to a 4πß(PC)-γ coincidence system using a gas flow proportional counter in 4π geometry coupled to a 76 × 76 mm NaI(Tl) crystal. The results for the γ-rays intensities at 80.57 and 1379.45 keV were 0.0651(11) and 0.00904(11), respectively.

The Production, Quality Control, and Characterization of ZED8, a CD8-Specific 89Zr-Labeled Immuno-PET Clinical Imaging Agent.

Immuno-PET is a molecular imaging technique utilizing positron emission tomography (PET) to measure the biodistribution of an antibody species labeled with a radioactive isotope. When applied as a clinical imaging technique, an immuno-PET imaging agent must be manufactured with quality standards appropriate for regulatory approval. This paper describes methods relevant to the chemistry, manufacturing, and controls component of an immuno-PET regulatory filing, such as an investigational new drug application. Namely, the production, quality control, and characterization of the immuno-PET clinical imaging agent, ZED8, an 89Zr-labeled CD8-specific monovalent antibody as well as its desferrioxamine-conjugated precursor, CED8, is described and evaluated. PET imaging data in a human CD8-expressing tumor murine model is presented as a proof of concept that the imaging agent exhibits target specificity and comparable biodistribution across a range of desferrioxamine conjugate loads.

Standardization of 142Pr activity concentration.

142Pr (praseodymium-142), a potential radionuclide for brachytherapy, was produced after irradiating high purity natural Pr2O3 powder in a research reactor. The irradiated powder was then dissolved in acids and diluted for measurement. Several radioactivity measurement methods were used in the standardization of 142Pr radionuclide. This work reports the results of standardization of 142Pr with CIEMAT/NIST efficiency tracing method, gamma spectrometry and a calibrated ionization chamber. The activity measured from different standardization methods are compatible with each other within the uncertainty limits. The CIEMAT/NIST efficiency tracing method gives the lowest uncertainty and is a reliable method for the standardization of this radionuclide.

Monitoring and Dose Assessment for Children Following a Radiation Emergency Part I: Reference Values for In Vitro Bioassay.

Following a radiation emergency, children may be internally contaminated by the radionuclide(s) involved. Timely assessment of the contamination informs the need for medical treatment for those persons who had significant intakes and reassures those whose intakes are not a medical concern. In vitro bioassay reference values for children of all ICRP age groups are derived for 30 contamination scenario/radionuclide combinations involving 13 radionuclides. These bioassay values are derived from an intake that leads to a 70-y committed effective dose of 50 mSv or a 30-d RBE-weighted absorbed dose to the lungs of 0.2 Gy-Eq, depending on which criterion is more strict. These values are presented in a collection of lookup tables that can be used directly as references.

Dynamic Radioactive Source for Evaluating and Demonstrating Time-dependent Performance of Continuous Air Monitors.

Evaluation of continuous air monitors in the presence of a plutonium aerosol is time intensive, expensive, and requires a specialized facility. The Radiation Protection Services Group at Los Alamos National Laboratory has designed a Dynamic Radioactive Source, intended to replace plutonium aerosol challenge testing. The Dynamic Radioactive Source is small enough to be inserted into the sampler filter chamber of a typical continuous air monitor. Time-dependent radioactivity is introduced from electroplated sources for real-time testing of a continuous air monitor where a mechanical wristwatch motor rotates a mask above an alpha-emitting electroplated disk source. The mask is attached to the watch's minute hand, and as it rotates, more of the underlying source is revealed. The measured alpha activity increases with time, simulating the arrival of airborne radioactive particulates at the air sampler inlet. The Dynamic Radioactive Source allows the temporal behavior of puff and chronic release conditions to be mimicked without the need for radioactive aerosols. The new system is configurable to different continuous air monitor designs and provides an in-house testing capability (benchtop compatible). It is a repeatable and reusable system and does not contaminate the tested air monitor. Test benefits include direct user control, realistic (plutonium) aerosol spectra, and iterative development of continuous air monitor alarm algorithms. Data obtained using the Dynamic Radioactive Source has been used to elucidate alarm algorithms and to compare the response time of two commercial continuous air monitors.

The Current Limits for Radionuclides in Food in Japan.

After the TEPCO Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, the current limits in Japan on the radionuclide contamination of food [100 Bq kg for general foods, 50 Bq kg for milk and infant foods, and 10 Bq kg for drinking water as radioactive cesium (Cs + Cs)] were established on the basis of an effective dose of 1 mSv y, consistent with international standards to mitigate the exposure of the general public to radiation. Measures that include recalling or restriction of food have been taken in cases when these limits were violated. As a result of these efforts, the actual effective doses of radioactive cesium (Cs + Cs) in foods approximately 1 y after the FDNPP accident were below 0.01 mSv y. However, there is little information on the current status of these limits in the literature, which necessitates a comprehensive review of the information that exists. In this paper, the concept behind the introduction of these limits, the methods by which they were derived, and the results of monitoring food accordingly, are reviewed. This information will be helpful in the case of a future accident, and it will also help to enhance the understanding of the current limits and to relieve the anxieties of the general public concerning radiation exposure from radionuclides in food.

The concept of minimum detectable activity of radionuclide activity meters and their suitability for routine quality control of radiopharmaceuticals. An experimental study.

Radionuclide activity meters ("dose calibrators") are ionization chambers designed to measure relatively high amount of activities which are normally contained in radiopharmaceuticals. However, in the current radiopharmacy practice, these radiation detectors have been proposed to be used in measurements of samples with lower activity, such as in routine quality control (QC) tests. To check the feasibility of such measurements, in this work we assessed the performance of four different devices in the lower range of detectability, by means of experimental measurements of a radioactive sample. Accuracy and precision of each device was evaluated as a function of the activity contained in the sample in order to estimate a threshold value, or minimum detectable activity (MDA), which, according to our operational definition, may be used to express the concept of Limit of Quantification (LoQ). Moreover, a generalized procedure for the estimation of the MDA was established, which, being device- and radionuclide-independent, it may be adopted by every laboratory. Our results showed a significant variability in the MDA achieved by different activity meters. Hence a single QC test may result feasible with one specific instrument, and not with another one. Moreover, feasibility depends also on the confidence level required for each test. For these reasons, each activity meter should be qualified for its MDA or LoQ by each laboratory according to a procedure such as that described in this paper.

Improvement of the WBC calibration of the Internal Dosimetry Laboratory of the CDTN/CNEN using the physical phantom BOMAB and MCNPX code.

The Laboratory of Internal Dosimetry of the Center for Development of Nuclear Technology (LDI/CDTN) is responsible for routine internal monitoring of occupationally exposed individuals. The determination of photon emitting radionuclides in the human body requires calibration of the detector in specific counting geometries. The calibration process uses physical phantoms containing certified activities of the radionuclides of interest. The objective of this work was to obtain calibration efficiency curves of the Whole Body Counter in operation at the LDI/CDTN using a BOMAB physical phantom and Monte Carlo simulations.

(210)Bi - from interference to advantage in (210)Pb determination with liquid scintillation counter.

A novel method for determination of (210)Pb activity concentration using a liquid scintillation counter (LSC) in environmental samples is presented. After radiochemical separation of (210)Pb on Eichrom Sr Resin column, the decay product (210)Bi starts to in-grow and interfere with the (210)Pb during measurement with LSC. Instead of eliminating this interference, a novel method utilises (210)Bi in-growth to improve the detection efficiency and subsequently to lower the minimum detectable activity (MDA). This allows for substantial reduction of the MDA compared to conventional methods.

(177)Lu: DDEP Evaluation of the decay scheme for an emerging radiopharmaceutical.

A new decay scheme evaluation using the DDEP methodology for (177)Lu is presented. Recently measured half-life measurements have been incorporated, as well as newly available γ-ray emission probabilities. For the first time, a thorough investigation has been made of the γ-ray multipolarities. The complete data tables and detailed evaluator comments are available through the DDEP website.

A novel method for the activity measurement of large-area beta reference sources.

A novel method has been developed for the activity measurement of large-area beta reference sources. It makes use of two emission rate measurements and is based on the weak dependence between the source activity and the activity distribution for a given value of transmission coefficient. The method was checked experimentally by measuring the activity of two ((60)Co and (137)Cs) large-area reference sources constructed from anodized aluminum foils. Measurement results were compared with the activity values measured by gamma spectrometry. For each source, they agree within one standard uncertainty and also agree within the same limits with the certified values of the source activity.

Standardisation and precise determination of the half-life of (44)Sc.

The half-life of the positron-emitter (44)Sc has been determined by following the decay rate with two measurement systems; an Ionisation Chamber and a HPGe detector. The combination of seven results gives a value of T1/2=4.042 (25)h, about 2% higher than the recommended value of T1/2=3.97 (4)h (Browne, 2011) and with a lower uncertainty. This radionuclide has also been standardised by coincidence counting, and liquid scintillation counting techniques. A (44)Ti/(44)Sc generator developed at CIEMAT was used to obtain the (44)Sc solutions used in all measurements.

Certified reference materials for radionuclides in Bikini Atoll sediment (IAEA-410) and Pacific Ocean sediment (IAEA-412).

The preparation and characterization of certified reference materials (CRMs) for radionuclide content in sediments collected offshore of Bikini Atoll (IAEA-410) and in the open northwest Pacific Ocean (IAEA-412) are described and the results of the certification process are presented. The certified radionuclides include: (40)K, (210)Pb ((210)Po), (226)Ra, (228)Ra, (228)Th, (232)Th, (234)U, (238)U, (239)Pu, (239+240)Pu and (241)Am for IAEA-410 and (40)K, (137)Cs, (210)Pb ((210)Po), (226)Ra, (228)Ra, (228)Th, (232)Th, (235)U, (238)U, (239)Pu, (240)Pu and (239+240)Pu for IAEA-412. The CRMs can be used for quality assurance and quality control purposes in the analysis of radionuclides in sediments, for development and validation of analytical methods and for staff training.

Consultative committee on ionizing radiation: Impact on radionuclide metrology.

In response to the CIPM MRA, and to improve radioactivity measurements in the face of advancing technologies, the CIPM's consultative committee on ionizing radiation developed a strategic approach to the realization and validation of measurement traceability for radionuclide metrology. As a consequence, measurement institutions throughout the world have devoted no small effort to establish radionuclide metrology capabilities, supported by active quality management systems and validated through prioritized participation in international comparisons, providing a varied stakeholder community with measurement confidence.

Dual nano-sized contrast agents in PET/MRI: a systematic review.

Nowadays molecular imaging plays a vital role in achieving a successful targeted and personalized treatment. Hence, the approach of combining two or more medical imaging modalities was developed. The objective of this review is to systematically compare recent dual contrast agents in Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) and in some cases Single photon emission computed tomography (SPECT)/MRI in terms of some their characteristics, such as tumor uptake, and reticuloendothelial system uptake (especially liver) and their relaxivity rates for early detection of primary cancer tumor. To the best of our knowledge, this is the first systematic and integrated overview of this field. Two reviewers individually directed the systematic review search using PubMed, MEDLINE and Google Scholar. Two other reviewers directed quality assessment, using the criteria checklist from the CAMARADES (Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies) tool, and differences were resolved by consensus. After reviewing all 49 studies, we concluded that a size range of 20-200 nm can be used for molecular imaging, although it is better to try to achieve as small a size as it is possible. Also, small nanoparticles with a hydrophilic coating and positive charge are suitable as a T2 contrast agent. According to our selected data, the most successful dual probes in terms of high targeting were with an average size of 40 nm, PEGylated using peptides as a biomarker and radiolabeled with copper 64 and gallium 68. Copyright © 2017 John Wiley & Sons, Ltd.

Practical correction method for impurities on activity measurements using isotope calibrators.

Radioactive impurities might cause significant error in the activity determination of a target nuclide using ionization chambers. In the present study, an impurity correction technique for (201)Tl sources was performed by applying two different responses of an IG12A20 and IG11N20 ionization chamber. This technique can be extended to another method in which an attenuation filter made of tin was used to obtain different responses of an argon filled IG12A20. The results obtained with these techniques were very consistent with each other and with the reference value within their uncertainty after making the impurity correction. Examples of (64)Cu activity determination were also shown.

Characterization of the energy response and backscatter contribution for two electronic personal dosimeter models.

We characterized the energy response of personal dose equivalent (Hp(10) in mrem) and the contribution of backscatter to the readings of two electronic personal dosimeter (EPD) models with radionuclides commonly used in a nuclear medicine clinic. The EPD models characterized were the RADOS RAD-60R, and the SAIC PD-10i. The experimental setup and calculation of EPD energy response was based on ANSI/HPS N13.11-2009. Fifteen RAD-60R and 2 PD-10i units were irradiated using (99m)Tc, (131)I, and (18)F radionuclides with emission energies at 140 keV, 364 keV, and 511 keV, respectively. At each energy, the EPDs output in Hp(10) [mrem] were recorded with 15 inch thick PMMA to simulate backscatter form the torso. Simultaneous free-in-air exposure rate measurements were also performed using two Victoreen ionization survey meters to calculate the expected EPD Hp(10) values per ANSI/HPS N13.11-2009. The energy response was calculated by taking the ratio of the EPD Hp(10) readings with the expected Hp(10) readings and a two-tailed z-test was used to determine the significance of the ratio deviating away from unity. The contribution from backscatter was calculated by taking the ratio of the EPD Hp(10) readings with and without backscatter material. A paired, two-tailed t-test was used to determine the significance of change in EPD Hp(10) readings. The RAD-60R mean energy response at 140 keV was 0.85, and agreed to within 5% and 11% at 364 and 511 keV, respectively. The PD-10i mean energy response at 140 keV was 1.20, and agreed to within 5% at 364 and 511 keV, respectively. On average, in the presence of acrylic, RAD-60R values increased by 32%, 12%, and 14%, at 140, 364, and 511 keV, respectively; all increases were statistically significant. The PD-10i increased by 25%, 19%, and 10% at 140 keV, 364 keV, and 511 keV, respectively; however, only the 140 keV measurement was statistically significant. Although both EPD models performed within the manufacturers' specifications of ± 25% in the energy ranges used, they fell outside of our criteria of 10% at lower energies, suggesting the need to calculate energy-dependent correction factors, depending on the intended EPD use.

Operational Check Source Recalibration.

A formal protocol whereby a segregated source is used for later quality control trending and recalibration of operational sources is described. The method is of potential use for any quality radioactive assay program where multiple sources may be in use such that long term loss in activity is possible and not readily detected and corrected using common statistical assessment criteria. The method relies upon a rigorous initial characterization effort that can later be credited to minimize error propagation during recalibration to monitor the overall uncertainty budget. A simple example attachment for use in written procedures is also provided.