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An activity standard for

Main text Since 1976, 30 laboratories have submitted 85 samples of 60Co to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)- K1.Co-60. Recently, the PTB (Germany), the NIST (United States), the SMU (Slovakia), the BARC (India), the LNE-LNHB (France), the POLATOM (Poland), the ENEA-INMRI (Italy), the NPL (United Kingdom), the LNMRI-IRD (Brazil), the NMISA (South Africa) and the ANSTO (Australia) participated in the comparison and the key comparison reference value (KCRV) has been updated. The degrees of equivalence between each equivalent activity measured in the SIR and the updated KCRV have been calculated and the results are given in the form of a table. A graphical representation is also given. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

We describe our progress toward a system to calibrate electrometers that measure currents from ionization chambers. The calibration system uses a $1\ \mathrm{G}\Omega$ standard resistor in series with a stable voltage source to generate calibration currents from 1 pA to 20 nA, traceable to quantum voltage and resistance standards through an 8-1/2 digit digital multimeter and the standard resistor. Expanded uncertainties ( $k=2$ ) of $100\times 10^{-6}$ or better for the calibration of the electrometer are needed for the ionization chamber measurements. We show our preliminary results including our initial calibration correction.

A suspension of (224)Ra adsorbed onto CaCO(3) microparticles shows promise for α-therapy of intracavitary micro-metastatic diseases. To facilitate accurate activity administrations, geometry-specific calibration factors for commercially available reentrant ionization chambers (ICs) have been developed for (224)RaCl(2) solutions and (224)Ra adsorbed onto CaCO(3) microparticles in suspension in ampoules, vials, and syringes. Ampoules and vials give IC responses consistent with each other to < 1%. Microparticles attenuation leads to a ≈ 1% to ≈ 2.5% reduction in response in the geometries studied.

A suspension of 224Ra adsorbed onto CaCO3 microparticles shows promise for α-therapy of intracavitary micro-metastatic diseases. To facilitate accurate activity administrations, geometry-specific calibration factors for commercially available reentrant ionization chambers (ICs) have been developed for 224RaCl2 solutions and 224Ra adsorbed onto CaCO3 microparticles in suspension in ampoules, vials, and syringes. Ampoules and vials give IC responses consistent with each other to

The complex decay scheme that makes 64Cu promising as both an imaging and therapeutic agent in medicine also makes the absolute measurement of its activity challenging. The National Institute of Standards and Technology (NIST) has completed a primary activity standardization of a 64CuCl2 solution using the 4πβ(LS)-γ(NaI) live-timed anticoincidence (LTAC) counting method with a combined standard uncertainty of 0.51 %. Two liquid scintillation (LS) counting methods were employed for confirmatory measurements. Secondary measurements were made by high-purity germanium detectors, pressurized ionization chambers (IC), and a well-type NaI(Tl) counter. Agreement between the LTAC-based standard and standards from other laboratories was established via IC calibration factors. Poor agreement between methods and with theoretical IC responses may indicate a need for improved β+/- branching probabilities and a better treatment of β+/- spectra.

A new nuclear forensic reference material has been characterized as a standard for radiochronometric determination of the model purification date for 137Cs sources. The purification date of a radioactive source is a potentially diagnostic nuclear forensic signature for determining the provenance of a radioactive material. Reference values have been measured for the attributes needed to use the 137Cs/137Ba chronometer: the molality (reported here as nmol g-1) of 137Cs and of the radiogenic portion of 137Ba in the material (hereafter referred to as 137Ba*). All measurement results were decay-corrected to represent the composition of the material on the reference date of July 7, 2011. The molality of 137Cs is (0.7915 ± 0.0073) nmol g-1; this value was calculated from the massic activity of 137Cs, (348.4 ± 3.0) kBq g-1, as measured in the NIST 4π-γ secondary standard ionization chamber (previously calibrated by 4π-(e+x)-γ-coincidence efficiency extrapolation counting) and the evaluated half-life of 137Cs, (30.05 ± 0.08) years. The molality of 137Ba*, (1.546 ± 0.024) nmol g-1, was measured by isotope dilution mass spectrometry using the measured relative proportion of 138Ba in the material to apply a correction for the 137Ba contribution from natural Ba. A model age of (47.04 ± 0.56) years, corresponding to a model purification date of June 22, 1964 with an expanded uncertainty of 200 days is calculated from the reference material values. This age is consistent with the date engraved on the capsule that contained the 137Cs starting material and with a prior independent determination of the model purification date. A full discussion of the uncertainties of the reference material values is included.

Background Most clinical measurements of radioactivity, whether for therapeutic or imaging nuclides, rely on commercial re-entrant ionization chambers ('dose calibrators'). The National Institute of Standards and Technology (NIST) maintains a battery of representative calibrators and works to link calibration settings ('dial settings') to primary radioactivity standards. Here, we provide a summary of NIST-determined dial settings for 22 radionuclides. Methods We collected previously published dial settings and determined some new ones using either the calibration curve method or the dialing-in approach. Results The dial settings with their uncertainties are collected in a comprehensive table. Conclusion In general, current manufacturer-provided calibration settings give activities that agree with National Institute of Standards and Technology standards to within a few percent.

In nuclear medicine, (68)Ge is used to generate (68)Ga for imaging by positron emission tomography (PET) and sealed sources containing (68)Ge/(68)Ga in equilibrium have been adopted as long-lived calibration surrogates for the more common PET nuclide, (18)F. We prepared several (68)Ge sources for measurement on a NaI(Tl) well counter and a pressurized ionization chamber, following their decay for 110 weeks (≈ 2.8 half-lives). We determined values for the (68)Ge half-life of T(1/2) = 271.14(15) d and T(1/2) = 271.07(12) d from the NaI(Tl) well counter and ionization chamber measurements, respectively. These are in accord with the current Decay Data Evaluation Project (DDEP) recommended value of T(1/2) = 270.95(26) d and we discuss the expected impact of our measurements on this value.

The National Institute of Standards and Technology (NIST) performed new standardization measurements for 64Cu. As part of this work the photon emission probability for the main gamma-ray line and the half-life were determined using several high-purity germanium (HPGe) detectors. Half-life determinations were also carried out with a NaI(Tl) well counter and two pressurized ionization chambers.

A standard for activity of (224)Ra in secular equilibrium with its progeny has been developed, based on triple-to-double coincidence ratio (TDCR) liquid scintillation (LS) counting. The standard was confirmed by efficiency tracing and 4παβ(LS)-γ(NaI(Tl)) anticoincidence counting, as well as by 4πγ ionization chamber and NaI(Tl) measurements. Secondary standard ionization chambers were calibrated with an expanded uncertainty of 0.62 % (k = 2). Calibration settings were also determined for a 5 mL flame-sealed ampoule on several commercial reentrant ionization chambers (dose calibrators).

A new nuclear forensic reference material has been characterized as a standard for radiochronometric determination of the model purification date for

A solution of 124I was standardized for activity by 4πβ(LS)-γ(NaI) live-timed anticoincidence (LTAC) counting, with confirmatory measurements by triple-to-double coincidence ratio (TDCR) and CIEMAT-NIST efficiency tracing (CNET) liquid scintillation counting. The LTAC-based standard was shown to be in agreement (within k = 1 uncertainties) with previous measurements at NIST and elsewhere. Calibration settings for radionuclide calibrators were determined and a discrepancy with literature values, partially due to a calibration methodology dependent upon an erroneous setting for 18F, was identified and explained.

Main text Since 1988, 3 laboratories have submitted 5 samples of 153Gd to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.Gd-153. Recently, the NIST (United States) participated in the comparison and the key comparison reference value (KCRV) has been updated. The degrees of equivalence between each equivalent activity measured in the SIR and the updated KCRV have been calculated and the results are given in the form of a table. A graphical presentation is also given. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

The National Institute of Standards and Technology (NIST) performed new standardization measurements for 124I. As part of this work the absolute photon emission intensity for the main gamma-rays of 124I were determined using several high-purity germanium (HPGe) detectors. In addition, the half-life for 124I was also determined using an HPGe detector. Ionization chamber measurements were performed for additional sources, but it was not possible to obtain a precise half-life value.

The National Institute of Standards and Technology (NIST) measured the internal pair production branching ratio of 90Y using two sources and four high purity germanium (HPGe) detectors to detect the resulting annihilation radiation. The internal pair production branching ratio determined from these measurements, (32.0 ± 1.5) × 10−6 (k = 1), agrees within 1 standard uncertainty with the recommended value of (32.6 ± 0.7) × 10−6 (k = 1) from the DDEP database.

A standard for activity of 224Ra in secular equilibrium with its progeny has been developed, based on triple-to-double coincidence ratio (TDCR) liquid scintillation (LS) counting. The standard was confirmed by efficiency tracing and 4παβ(LS)-γ(NaI(Tl)) anticoincidence counting, as well as by 4πγ ionization chamber and NaI(Tl) measurements. Secondary standard ionization chambers were calibrated with an expanded uncertainty of 0.62% (k = 2). Calibration settings were also determined for a 5 mL flame-sealed ampoule on several commercial reentrant ionization chambers (dose calibrators).

This report summarises the results for the new BIPM.RI(II)-K1.Ge-68 comparison. Six metrology institutes have participated, enabling the first value of the key comparison reference value(KCRV) to be determined. The KCRV was calculated using the power-moderated weighted mean and the results. A link has been made to the CCRI(II)-K2.Ge-68 comparison held in 2015 through the NIST, NIM,IRA-METAS and the LNE-LNHB who participated in both comparisons. One NMI used the K2 comparison to update their degree of equivalence. The degrees of equivalence between each equivalent activity measured in the International Reference System (SIR) and the KCRV have been calculated and the results are given in the form of a table for the remaining five NMIs in the BIPM.RI(II)-K1.Ge-68 comparison and the 12 other participants in the CCRI(II)-K2.Ge-68 comparison. A graphical presentation is also given. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Proceedings of the 21st International Conference on Radionuclide Metrology and its Applications (ICRM), May 15-19, 2017, Buenos Aires, Argentina. Organizer: Argentinian National Atomic Energy Commission; International audience; An international key comparison, identifier CCRI(II)-K2.Ge-68, has been performed. The National Institute of Standards and Technology (NIST) served as the pilot laboratory, distributing aliquots of a $^{68}$Ge/$^{68}$Ga solution. Results for the activity concentration, CA, of $^{68}$Ge at a reference date of 12h00 UTC 14 November 2014 were submitted by 17 laboratories, encompassing many variants of coincidence methods and liquid-scintillation counting methods. The first use of 4π(Cherenkov)β-γ coincidence and anticoincidence methods in an international comparison is reported. One participant reported results by secondary methods only. Two results, both utilizing pure liquid-scintillation methods, were identified as outliers. Evaluation using the Power-Moderated Mean method results in a proposed Comparison Reference Value (CRV) of 621.7(11) kBq g$^{−1}$, based on 14 results. The degrees of equivalence and their associated uncertainties are evaluated for each participant. Several participants submitted 3.6 mL ampoules to the BIPM to link the comparison to the International Reference System (SIR) which may lead to the evaluation of a Key Comparison Reference Value and associated degrees of equivalence.

As a result of a recent change in the National Institute of Standards and Technology (NIST) activity standard for 18F, we have determined new relative response ratios for a 68Ge solid epoxy mock syringe source used in activity calibrators as a long-lived substitute for 18F. New standardized solutions of each radionuclide were used to determine the response ratios while maintaining traceability to national standards. This work updates our previously published data from 2010. Methods: Following our previously published methodology, solution-filled mock syringe sources, identical in geometry to the solid 68Ge epoxy calibration source currently on the market, were prepared using NIST-calibrated solutions of 68GeCl4 and 18F-FDG and directly compared in several models of activity calibrators to determine empirically the relative response ratios for these 2 radionuclides. Results: The new relative response ratios measured in this study reflect the change in 18F activity measurements that arise from the recent −4% change in the NIST activity standard. The results allow the 68Ge activity of the mock syringe source to be expressed in terms of equivalent 18F activity, with a relative combined standard uncertainty of about 0.8% for the activity calibrators used in this study. Conclusion: This work revises our previously derived relative response ratios for 18F and 68Ge by −3.7%, allowing users of the commercial mock syringe surrogate source to calibrate their activity calibrators in a way that is consistent with the recent change in the NIST 18F standard.

Dose calibrator dial settings reported by NIST in 2010 (ARI, v. 68, p. 1367) are now known to give erroneously low (by 10%) activity readings. The original determinations were based on a chain of calibrations; a broken link in this chain was recently discovered. New calibration factors (i.e., dial settings), directly linked to updated NIST primary standards, are reported here. In addition, the raw data used to derive the factors reported in 2010 are revisited. The validity of the reevaluation is established via comparison with the new experiments and revised calibration factors for numerous clinical geometries are reported. The main conclusions of the 2010 report regarding geometry effects remain valid.

The currently published 223 Ra gamma-ray emission probabilities display a wide variation in the values depending on the source of the data. The National Institute of Standards and Technology performed activity measurements on a 223 Ra solution that was used to prepare several sources that were used to determine the photon emission probabilities for the main gamma-rays of 223 Ra in equilibrium with its progeny. Several high purity germanium (HPGe) detectors were used to perform the gamma-ray spectrometry measurements.

Tests for chemical stability were carried out on carrier-added (68)Ge solutions prepared and calibrated in 2007 and 2011 to evaluate the suitability of the specific composition as a potential Standard Reference Material. Massic count rates of the stored solutions were measured using a NaI(Tl) well counter before and after gravimetric transfers. The present activity concentration of the 2007 solution was also measured using live-timed anticoincidence counting (LTAC) and compared to the 2007 calibrated value. The well counter data indicated no change in massic count rate to within uncertainties for either solution. The LTAC measurements gave a difference of -0.49% in the activity concentration 2007 solution over 7 years. However, the uncertainty in the decay correction over that time, due to the uncertainty in the (68)Ge half-life, accounted for the majority (0.67% out of 0.83%) of the standard uncertainty on the activity concentration. The results indicate that these carrier-added solutions are stable with regard to potential activity losses over several half-lives of (68)Ge.

Source self-attenuation for solutions of (57)Co of varying density and carrier concentration was measured in nine re-entrant ionization chambers maintained at NIST. The magnitude of the attenuation must be investigated to determine whether a correction is necessary in the determination of the activity of a source that differs in composition from the source used to calibrate the ionization chamber. At our institute, corrections are currently made in the measurement of (144)Ce, (109)Cd, (67)Ga, (195)Au, (166)Ho, (177)Lu, and (153)Sm. This work presents the methods used as recently applied to (57)Co. A range of corrections up to 1% were calculated for dilute to concentrated HCl at routinely used carrier concentrations.

Calibration factors for commercial ionization chambers (i.e. dose calibrators) were determined for a solution of 123I; the activity was based on the 1976 NBS standard. A link between the NIST standard and the International Reference System (SIR) was established. The two major U.S. dose calibrator manufacturers recommend oppositely biased calibration factors, giving a spread of 11.3% in measured activities. With modern quantitative imaging techniques capable of ≤10% accuracy, this bias for a SPECT nuclide is highly significant.

We have developed a methodology to calibrate the (68)Ge activity concentration in large (9L) cylindrical epoxy phantoms in a way that is traceable to national standards. The method was tested on two prototype cylindrical phantoms that are being used in a clinical trial and gave (68)Ge activity concentration values with combined standard uncertainties of about 1.1%. Imaging data from the phantoms using a calibrated PET-CT scanner gave values consistent with the calibrated activity concentrations within experimental uncertainties.

A new primary standardization of 18 F by NIST is reported. The standard is based on live-timed beta-gamma anticoincidence counting with confirmatory measurements by three other methods: ( i ) liquid scintillation (LS) counting using CIEMAT/NIST 3 H efficiency tracing; ( ii ) triple-to-double coincidence ratio (TDCR) counting; and ( iii ) NaI integral counting and HPGe γ-ray spectrometry. The results are reported as calibration factors for NIST-maintained ionization chambers (including some “dose calibrators”). The LS-based methods reveal evidence for cocktail instability for one LS cocktail. Using an ionization chamber to link this work with previous NIST results, the new value differs from the previous reports by about 4%, but appears to be in good agreement with the key comparison reference value (KCRV) of 2005.

Liquid scintillation (LS) counting was undertaken as part of the primary standardization of (223)Ra. Radium-223 decays with a half life of 11.43 d through a chain of shorter-lived daughter radionuclides, resulting in five alpha decays and three beta decays. The CIEMAT/NIST method of tritium efficiency tracing was employed, with the beta efficiencies being calculated using the program CN2004, developed by the Physikalisch-Technische Bundesanstalt (PTB). The total calculated LS efficiency, considering all daughter radionuclides, was approximately 598%. Separate experiments were performed to rule out loss of the 3.96 s (219)Ra daughter from the cocktail and possible counting loss of the 1.78 ms (215)Po daughter due to LS counter dead-time. No loss was observed in either experiment. In the final experiment an expanded uncertainty (k=2) of 0.55% was achieved. Results were in excellent agreement with confirmatory measurements performed by 2pialpha proportional counting. However, results are not in agreement with methods based on gamma ray measurements.

We have developed a methodology for calibrating (68)Ge radioactivity content in a commercially available calibration source for activity calibrators in a way that is traceable to the national standard. Additionally, the source was cross-calibrated for equivalent (18)F content by direct comparison with the national standard for (18)F in the same geometry.Sources containing standardized (68)GeCl(4) or (18)F-FDG solutions were prepared at the National Institute of Standards and Technology (NIST) with mock syringe blanks used in the construction of a commercially available epoxy-based (68)Ge calibration source. These sources and several NIST-constructed epoxy-based (68)Ge mock syringes were then used as artifact standards to determine calibration factors for NIST-maintained activity calibrators and secondary standard ionization chambers to enable calibration of the actual commercial sources. A direct comparison between the solution-based (68)Ge sources and the (18)F-FDG sources allowed for an empiric determination of the relative response for these radionuclides in several commercial activity calibrators. Potential measurement effects due to differences between the solution composition and the epoxy and theoretic (68)Ge-to-(18)F response ratios were studied by Monte Carlo simulation.The calibration factors developed in this study enabled NIST to calibrate epoxy-based mock syringe sources with a relative combined standard uncertainty of 0.52%. The direct comparisons of the (68)Ge and (18)F standards in the various ionization chambers allowed the activity to be expressed in terms of equivalent (18)F activity with a relative combined standard uncertainty of about 0.9%.The ability for NIST to calibrate these epoxy-based mock syringes enabled, for the first time to our knowledge, the direct traceability to the national (68)Ge standard to be established for this type of source. Through a direct comparison with the NIST (18)F standard, the determination of the relative response ratios in activity calibrators enabled the equivalent (18)F activity to be determined in a way that was also traceable to the national (18)F activity standard.

This paper discusses the calibration of Capintec radionuclide calibrators for the measurement of (18)F in the pharmacy and clinic. In support of a planned regional comparison, a secondary laboratory was set up at Oak Ridge National Laboratories in Oak Ridge, TN. The laboratory was used to prepare 1mL (18)F-fluorodeoxyglucose sources in 3mL plastic BD syringes (Becton, Dickinson and Company, Franklin Lakes, New Jersey, USA) and to determine dial settings in three models of radionuclide calibrators. Measurements were verified by comparing radionuclide calibrator measurements of a 5mL ampoule source with previous results. The CIEMAT/NIST method of tritium efficiency tracing was used for activity determinations.

A blind performance test was conducted to evaluate dose-calibrator measurements at nuclear pharmacies in the United States (US). Two test-sample geometries were chosen to represent those used for measurements of 90Y-ibritumomab tiuxetan (ZEVALIN). The radioactivity concentration of test-samples was verified by the US National Institute of Standards and Technology. Forty-five results were reported by 10 participants. Eighty percent of reported values were within the US Pharmacopoeia content standard (+/-10%) for 90Y-ZEVALIN. All results were within US Nuclear Regulatory Commission conformance limits (+/-20%) for defining therapeutic misadministrations.

Dose calibrator dial settings reported by NIST in 2010 (ARI, v. 68, p. 1367) are now known to give erroneously low (by 10%) activity readings. The original determinations were based on a chain of calibrations; a broken link in this chain was recently discovered. New calibration factors (i.e., dial settings), directly linked to updated NIST primary standards, are reported here. In addition, the raw data used to derive the factors reported in 2010 are revisited. The validity of the reevaluation is established via comparison with the new experiments and revised calibration factors for numerous clinical geometries are reported. The main conclusions of the 2010 report regarding geometry effects remain valid.

(90)Y microspheres are important therapeutic radiopharmaceuticals used in the treatment of liver cancer through a process known as selective internal radiation therapy. SIR-spheres is a radiopharmaceutical product that is comprised of (90)Y microspheres suspended in sterile, pyrogen-free water for injection into patients. It is necessary to establish for the SIR-spheres production the capability of accurately measuring the activity of this product to a traceable national measurement standard. An activity standard for SIR-spheres was developed from a standard for (90)Y solution, employing a highly quantifiable chemical digestion process. Calibration factors for the manufacturer's ionisation chambers were determined for 1 and 5 ml of the SIR-spheres product placed in Wheaton vials, for both 34% and 44% of (90)Y microsphere concentration.

The effect of measurement geometry on the determination of the activity of solutions containing 125 I for use in brachytherapy applications has been investigated for 5 mL plastic syringes and 2 mL conical glass dose vials as a function of filling mass. New dial settings for the syringes over a filling mass range of 1 to 3 g have been determined to be 497±8 and 469±8 (expanded, k=2, uncertainties) for the NIST Capintec CRC-12 and Capintec CRC-35R, respectively, with any effect due to the filling mass lying within the uncertainty in the activity calibration. A filling mass effect was observed in the dose vials, causing a 10.5% reduction in the chamber response from a 2 g filling mass to 1 g. Dial settings at 2 g were experimentally found to be 143±2 and 135±2 (expanded uncertainties) for the NIST Capintec CRC-12 and Capintec CRC-35R, respectively. The appropriate dial settings for the same vials with a 1 g filling mass were found to be 120±2 and 114±2 for CRC-12 and CRC-35R, respectively. Differences of up to ±45% in the activity determination were observed between values obtained with the manufacturer’s recommended setting and the settings obtained experimentally for each specific geometry. Calibration factors were also determined for a Vinten 671 Radionuclide Calibrator, giving values of 0.226±0.009 pA ⋅ MBq −1 and 0.231±0.004 pA ⋅ MBq −1 (expanded uncertainties), respectively, for the 1 and 2 g dispensings. This study demonstrates that experimentally determined calibration factors for the exact measurement geometry are necessary when measuring radionuclides in configurations other than the manufacturer’s standard geometry, especially when nuclides that emit low-energy radiations are involved.

In 2016, comparisons of activity measurements of 18F and 64Cu using the Transfer Instrument of the International Reference System (SIRTI) took place at the National Institute of Standards and Technology (NIST, USA). This is the first SIRTI comparison for 64Cu. Ampoules containing about 27 kBq of 18F and 100 kBq of 64Cu solutions were measured in the SIRTI for about 5 and 1.5 half-lives, respectively. The NIST standardized the activity in the ampoules by ionization chamber measurements traceable to 4π(LS)β−γ anticoincidence measurements. The comparisons, identifiers BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Cu-64, are linked to the corresponding BIPM.RI(II)-K1.F-18 and BIPM.RI(II)-K1.Cu-64 comparisons and degrees of equivalence with the respective key comparison reference values have been evaluated. The NIST replaces its earlier degree of equivalence for 18F obtained in the frame of the CCRI(II)-K3.F-18 comparison in 2001. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Commercial reentrant ionization chambers (‘dose calibrators’) have become the de facto standard instrument for making radioactivity measurements in the radiopharmaceutical industry. Accurate activity measurements, however, depend on the application of the correct calibration factor (dial setting) for the radionuclide in the exact measurement geometry for that particular instrument. Two methods are described for the experimental determination of dial settings for the Capintec CRC-12 dose calibrator. Using these methods, we have determined new calibration factors for 18 F, 62 Cu, 186 Re and 188 Re in several geometries. These new factors are presented, along with previously determined settings, for nuclides commonly used in nuclear medicine. The differences between the calibration factors for the different geometries, as well as the differences between the manufacturer's recommended setting underscore the need for empirically determined dose calibrator settings.

The Positron Emission Tomography agent 62Cu Pyruvaldehyde Bis(N4-methyl)thiosemicarbazone (PTSM) has been standardized by the National Institute of Standards and Technology (NIST) using 4 pi beta liquid scintillation counting with 3H-standard efficiency tracing. Using a measurement model developed at NIST for the determination of experimental dose calibrator dial settings for short-lived radionuclides, the correct dial settings for 62CuPTSM in a clinically useful geometry (a 35 ml plastic syringe containing 33 ml of solution) as well as the standard NIST 5 ml glass ampoule have been elucidated. This measurement model is fully described, as is the treatment of associated uncertainties. The correct instrument settings for the NIST Capintec CRC-12 re-entrant ionization chamber ('dose calibrator') were found to be '499 +/- 6' and '489 +/- 8', respectively, for the syringe and ampoule geometries. The stated uncertainties are expanded (k = 2) uncertainties. The expanded uncertainties in the measured activity arising from these new dial settings are +/- 0.8% and +/- 1.4%, respectively, for the syringe and ampoule. The measured activities using these settings are lower than those obtained from the manufacture's recommended setting of '448' by 9.7% for the syringe and 7.7% for the ampoule, and underscore the need for experimental verification of the dose calibrator settings for each radionuclide and each geometry used in the clinic.

The uses of β-particle emitting radionuclides in therapeutic medicine are rapidly expanding. To ensure the accurate assays of these nuclides prior to administration, radioactivity standards are needed. The National Institute of Standards and Technology (NIST), the national metrological standards laboratory for the United States, uses high-efficiency liquid scintillation counting to standardize solutions of such β emitters, including 32 P, 90 Sr/ 90 Y, and 188 Re. Additional measurements are made on radionuclidic impurities, half lives, and other decay-scheme parameters (such as branching decay ratios or γ-ray abundances) using HPGe detectors and reentrant ionization chambers. Following such measurements at NIST, standards are disseminated in three ways: Standard Reference Materials (SRMs), calibrations for source manufacturers, and calibration factors for commercial instruments. Uncertainties in the activity calibrations for these nuclides are of the order of ±0.5% (at approximately 1–standard deviation confidence intervals).

Solutions containing the potential bone pain palliation radionuclide 117mSn, in chloride form and as a diethylenetriaminepentaacetate (DTPA) complex, have been standardized by 4 pi beta liquid scintillation (LS) spectrometry and 4 pi gamma-ray spectrometry. Massic activities of the stock solutions were measured in order to determine dose calibrator settings for the solutions using commercial dose calibrators. Excellent agreement in the measurement of solution massic activity between the two techniques was achieved. The massic activity of 117mSnCl4 stock solution was found to be 38.62 +/- 0.23 MBq g-1 and 38.81 +/- 0.94 MBq g-1 with LS spectrometry and 4 pi gamma-ray spectrometry respectively. The respective values of the massic activity of the 117mSnDTPA stock solution with LS spectrometry and 4 pi gamma-ray spectrometry were 39.35 +/- 0.23 MBq g-1 and 39.70 +/- 0.96 MBq g-1. Impurities were analyzed in several solutions and found to have emission rates on the order of 10(-4) to 10(-6) of the rate of the 117mSn emission at the end-of-bombardment. The largest impurities came from 113Sn and 125Sn, the activation products of isotopic impurities present in the 117Sn target. The relative proportions of the various impurities were found to be highly dependent upon the source of 117Sn target material. The implications of choice of half-life used in the decay correction of 117mSn are discussed.

Calibration factors for commercial ionization chambers (i.e. dose calibrators) were determined for a solution of (123)I; the activity was based on the 1976 NBS standard. A link between the NIST standard and the International Reference System (SIR) was established. The two major U.S. dose calibrator manufacturers recommend oppositely biased calibration factors, giving a spread of 11.3% in measured activities. With modern quantitative imaging techniques capable of ≤10% accuracy, this bias for a SPECT nuclide is highly significant.

The International Atomic Energy Agency (IAEA) has organized an international comparison to assess Single Photon Emission Computed Tomography (SPECT) image quantification capabilities in 12 countries. Iodine-131 was chosen as the radionuclide for the comparison because of its wide use around the world, but for logistical reasons solid (133)Ba sources were used as a long-lived surrogate for (131)I. For this study, we designed a set of solid cylindrical sources so that each site could have a set of phantoms (having nominal volumes of 2 mL, 4 mL, 6 mL, and 23 mL) with traceable activity calibrations so that the results could be properly compared. We also developed a technique using two different detection methods for individually calibrating the sources for (133)Ba activity based on a National standard. This methodology allows for the activity calibration of each (133)Ba source with a standard uncertainty on the activity of 1.4 % for the high-level 2-, 4-, and 6-mL sources and 1.7 % for the lower-level 23 mL cylinders. This level of uncertainty allows for these sources to be used for the intended comparison exercise, as well as in other SPECT image quantification studies.

Radionuclides are increasingly used in therapeutic nuclear medicine. The CIEMAT/NIST method of standardizing high-energy beta-particle emitters is being applied to a list of candidate radionuclides developed by the US nuclear medicine community. Standards and standard methods are needed by the pharmaceutical manufacturers in North America before these nuclides can be widely distributed. Solutions standardized by liquid-scintillation counting are used to establish counting efficiencies for Cerenkov counting and NaI(T1) well crystals, and potentiometer settings for commercial radionuclide calibrators. Results are presented for a number of beta-particle-emitting radionuclides.

The National Institute of Standards and Technology (NIST) maintains a program for the establishment and dissemination of activity measurement standards in nuclear medicine. These standards are disseminated through Standard Reference Materials (SRMs), Calibration Services, radionuclide calibrator settings, and the NIST Radioactivity Measurement Assurance Program (NRMAP, formerly the NEI/NIST MAP). The MAP for the radiopharmaceutical industry is described here. Consolidated results show that, for over 3600 comparisons, 96% of the participants' results differed from that of NIST by less than 10%, with 98% being less than 20%. Individual radionuclide results are presented from 214 to 439 comparisons, per radionuclide, for (67)Ga, (90)Y, (99m)Tc, (99)Mo, (111)In, (125)I, (131)I, and (201)Tl. The percentage of participants results within 10% of NIST ranges from 88% to 98%.

An international Key Comparison of (177)Lu has recently been carried out. Twelve laboratories performed assays for radioactivity content on aliquots of a common master solution of (177)Lu, leading to eleven results submitted for entry into the Key Comparison Database of the Mutual Recognition Arrangement. A proposed Comparison Reference Value (CRV) was calculated to be 3.288(4)MBq/g using all eleven results. Degrees of equivalence and their uncertainties were calculated for each laboratory based on the CRV. Most of the values reported by the participating laboratories were within 0.6% of the CRV.

A system for intercomparing standard solutions of pure beta-particle emitting radionuclides is described. The CIEMAT/NIST technique of beta-particle efficiency tracing is based on establishing a parameter in a simple calculational model, using a 3 H standard with comparable quenching. To produce a 3 H-in-scintillator standard which is reasonably stable over the period of the measurements, we first standardized 3 H-hexadecane solution by comparison with 3 H-water standardized by gas counting. In the second phase of the work, the 3 H-hexadecane solution was used to standardize 14 C-hexadecane and 99 Tc-tricaprylamine (TCA). Measurements were made under similar geometrical and quenching conditions for each radionuclide with a commercial scintillator and a conventional liquid-scintillation counter with two phototubes operating in coincidence. The technique was then tested at different sites in the area using a set of flame-sealed vials and state-of-the-art liquid-scintillation counters. Initial results for the 99 Tc-TCA and the 1981 99 Tc, Standard Reference Material (SRM) 4288 show an agreement to within 0.30%.

A new secondary measuring system for 222 Rn-in-air that can be used as a very efficacious transfer calibration standard for measurement intercomparisons between laboratories has been developed and extensively tested. The system is based on measurements of the photon emission rate of radon samples contained in spherical 35-mL glass ampoules with a NaI(Tl) well counter. The system is calibrated against the NIST pulse-ionization-chamber (PIC) national radon measuring system, and has an overall uncertainty of approximately 2 percent. An international intercomparison of 11 laboratories, including NIST, using this system was performed.

Ra-223 is a bone-seeking alpha emitter currently being evaluated as a radiopharmaceutical. Concurrent with the primary standardization, NIST established that calibration factors currently used for radionuclide calibrators in the clinical setting give readings 5.7–8.7% higher than the NIST calibrated activity. This work describes the determination of calibration factors specific to dose vials and syringes. Using the calibration factors derived with standard ampoules to measure syringe activities can give readings up to 3.6% too high.

Rhenium-186 has been standardized for activity by the CIEMAT/NIST method of 4πβ liquid-scintillation efficiency tracing with tritium, with an uncertainty (equivalent to 1 SD) of 1.61%. Half-life measurements with a pressurized ionization chamber give a T 1 2 = 89.25 ± 0.07 h . Photon emission rates were measured with semiconductor detectors, and the probability of emission of the principal γ-ray at 137 keV was found to be P7 = 0.0945 ± 0.0016.