A Review of NIST Primary Activity Standards for (18)F: 1982 to 2013.

The new NIST activity standardization for (18)F, described in 2014 in Applied Radiation and Isotopes (v. 85, p. 77), differs from results obtained between 1998 and 2008 by 4 %. The new results are considered to be very reliable; they are based on a battery of robust primary measurement techniques and bring the NIST standard into accord with other national metrology institutes. This paper reviews all ten (18)F activity standardizations performed at NIST from 1982 to 2013, with a focus on experimental variables that might account for discrepancies. We have identified many possible sources of measurement bias and eliminated most of them, but we have not adequately accounted for the 1998-2008 results.

Liquid scintillation efficiencies, gamma-ray emission intensities, and half-life for Gd-153.

Gadolinium-153 was standardized for activity by live-timed anticoincidence counting and an ampoule was submitted to the international reference system (SIR). Absolute emission intensities for the main γ rays were determined with calibrated high-purity germanium (HPGe) and lithium-drifted silicon (Si(Li)) detectors. A revised decay scheme is indicated, with no probability of direct electron capture to the 153Eu ground state. Triple-to-double coincidence ratio (TDCR) efficiency curves indicate that the revised decay scheme is consistent with experiment. Half-life measurements agree with a previous NIST determination and show no sensitivity to chemical environment.

Activity standard and calibrations for 227Th with ingrowing progeny.

Thorium-227 was separated from its progeny and standardized for activity by the triple-to-double coincidence ratio (TDCR) method of liquid scintillation counting. Confirmatory liquid scintillation-based measurements were made using efficiency tracing with 3H and live-timed anticoincidence counting (LTAC). The separation time and the efficiency of the separation were confirmed by gamma-ray spectrometry. Calibrations for reentrant pressurized ionization chambers, including commercial radionuclide calibrators, and a well-type NaI(Tl) detector are discussed.

Primary standardization of 212Pb activity by liquid scintillation counting.

An activity standard for 212Pb in equilibrium with its progeny was realized, based on triple-to-double coincidence ratio (TDCR) liquid scintillation (LS) counting. A Monte Carlo-based approach to estimating uncertainties due to nuclear decay data (branching ratios, beta endpoint energies, γ-ray energies, and conversion coefficients for 212Pb and 208Tl) led to combined standard uncertainties ≤ 0.20 %. Confirmatory primary measurements were made by LS efficiency tracing with tritium and 4παß(LS)-γ(NaI(Tl)) anticoincidence counting. The standard is discussed in relation to current approaches to 212Pb activity calibration. In particular, potential biases encountered when using inappropriate radionuclide calibrator settings are discussed.

Ra-224 activity, half-life, and 241 keV gamma ray absolute emission intensity: A NIST-NPL bilateral comparison.

The national metrology institutes for the United Kingdom (UK) and the United States of America (USA) have compared activity standards for 224Ra, an α-particle emitter of interest as the basis for therapeutic radiopharmaceuticals. Solutions of 224RaCl2 were assayed by absolute methods, including digital coincidence counting and triple-to-double coincidence ratio liquid scintillation counting. Ionization chamber and high-purity germanium (HPGe) γ-ray spectrometry calibrations were compared; further, a solution was shipped between laboratories for a direct comparison by HPGe spectrometry. New determinations of the absolute emission intensity for the 241 keV γ ray (Iγ = 4.011(16) per 100 disintegrations of 224Ra) and of the 224Ra half-life (T1/2 = 3.6313(14) d) are presented and discussed in the context of previous measurements and evaluations.

Radionuclide calibrator responses for 224Ra in solution and adsorbed on calcium carbonate microparticles.

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 <1%. Microparticles attenuation leads to a ≈1% to ≈2.5% reduction in response in the geometries studied.

Primary standardization of 224Ra activity by liquid scintillation counting.

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 4παß(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 performance evaluation of 90Y dose-calibrator measurements in nuclear pharmacies and clinics in the United States.

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.

An update on 'dose calibrator' settings for nuclides used in nuclear medicine.

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.

Two determinations of the Ge-68 half-life.

In nuclear medicine, 68Ge is used to generate 68Ga for imaging by positron emission tomography (PET) and sealed sources containing 68Ge/68Ga in equilibrium have been adopted as long-lived calibration surrogates for the more common PET nuclide, 18F. We prepared several 68Ge 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 68Ge half-life of T1/2 = 271.14(15) d and T1/2 = 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 T1/2 = 270.95(26) d and we discuss the expected impact of our measurements on this value.

A reference material for evaluation of 137 Cs radiochronometric measurements.

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.

Assessing the 210At impurity in the production of 211At for radiotherapy by 210Po analysis via isotope dilution alpha spectrometry.

A method for assessing the impurity 210At in cyclotron-produced 211At via isotope dilution alpha spectrometry is presented. The activity of 210At is quantified by measuring the activity of daughter nuclide 210Po. Counting sources are prepared by spontaneous deposition of Po on a silver disc. Activity of 210At (at the time of 210Po maximum activity) is found to be 83.5+/-9.0 Bq, corresponding to an atom ratio (210At:211At at the time of distillation) of 0.010+/-0.007% (k=2). The method produces high-quality alpha spectra, with baseline alpha-peak resolution and chemical yields of greater than 85%.

Source self-attenuation in ionization chamber measurements of (57)Co solutions.

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.

Impact of Recent Change in the National Institute of Standards and Technology Standard for 18F on the Relative Response of 68Ge-Based Mock Syringe Dose Calibrator Standards.

UNLABELLED: As a result of a recent change in the National Institute of Standards and Technology (NIST) activity standard for (18)F, we have determined new relative response ratios for a (68)Ge solid epoxy mock syringe source used in activity calibrators as a long-lived substitute for (18)F. 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 (68)Ge epoxy calibration source currently on the market, were prepared using NIST-calibrated solutions of (68)GeCl4 and (18)F-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 (18)F activity measurements that arise from the recent -4% change in the NIST activity standard. The results allow the (68)Ge activity of the mock syringe source to be expressed in terms of equivalent (18)F 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 (18)F and (68)Ge 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 (18)F standard.

Secondary standards for ²²³Ra revised.

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 measurement of activity contained in a 32P stainless-steel stent by destructive assay.

Destructive assays of stainless-steel stents containing 32P were performed. Prior to assay, 24 stents were intercompared on a NaI(Tl) well-type crystal. A subset of stents were then digested in a suitable carrier solution by the addition of concentrated hydrofluoric acid. The final solution was measured by the CIEMAT/NIST tritium efficiency tracing method for liquid scintillation counting. A separate experiment was performed which indicated no loss of activity during stent digestion. Expanded (k = 2) uncertainties on stent activity ranged from 1.0% to 2.6%.

The standardization of 188W/188Re by 4pi beta liquid scintillation spectrometry with the CIEMAT/NIST 3H-standard efficiency tracing method.

The massic activity of a solution containing 188W in equilibrium with its daughter, 188Re, has been standardized by the National Institute of Standards and Technology using 4pi beta liquid scintillation counting with efficiency tracing using the CIEMAT NIST method. Confirmatory measurements were carried out with gamma-ray spectrometry using high purity germanium detectors and a 4pi gamma NaI(Tl) system. A calibration factor of 1.68 MBq pA(-1) +/-0.03 MBq pA(-1) (expanded, k = 2, uncertainty) for the 188W in the solution was determined, along with correction factors for activity determinations using Capintec dose calibrators. A half-life value of 69.78 d +/- 0.05 d (standard uncertainty) was determined by measurement in the NIST 4pi gamma ionization chamber and is consistent with currently recommended values.

Dose calibrator manufacturer-dependent bias in assays of ¹²³I.

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 NIST radioactivity measurement assurance program for the radiopharmaceutical industry.

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%.

The effect of impurities on calculated activity in the triple-to-double coincidence ratio liquid scintillation method.

In the triple-to-double coincidence ratio (TDCR) method of liquid scintillation counting, unaccounted or improperly accounted impurities can result in lower-than-expected or higher-than-expected recovered activities, depending on the counting efficiency of the nuclide of interest, the counting efficiency of the radionuclidic impurity, and the amount of impurity present. We describe these general dependences using a simple model. The trends predicted by the model are tested experimentally using a series of mixed (241)Am/(3)H and (63)Ni/(3)H sources. An "impurity surface" is derived to facilitate an intuitive grasp of impurity phenomena in TDCR.