Revision of the NIST Standard for (223)Ra: New Measurements and Review of 2008 Data.

After discovering a discrepancy in the transfer standard currently being disseminated by the National Institute of Standards and Technology (NIST), we have performed a new primary standardization of the alpha-emitter (223)Ra using Live-timed Anticoincidence Counting (LTAC) and the Triple-to-Double Coincidence Ratio Method (TDCR). Additional confirmatory measurements were made with the CIEMAT-NIST efficiency tracing method (CNET) of liquid scintillation counting, integral γ-ray counting using a NaI(Tl) well counter, and several High Purity Germanium (HPGe) detectors in an attempt to understand the origin of the discrepancy and to provide a correction. The results indicate that a -9.5 % difference exists between activity values obtained using the former transfer standard relative to the new primary standardization. During one of the experiments, a 2 % difference in activity was observed between dilutions of the (223)Ra master solution prepared using the composition used in the original standardization and those prepared using 1 mol·L(-1) HCl. This effect appeared to be dependent on the number of dilutions or the total dilution factor to the master solution, but the magnitude was not reproducible. A new calibration factor ("K-value") has been determined for the NIST Secondary Standard Ionization Chamber (IC "A"), thereby correcting the discrepancy between the primary and secondary standards.

Absolute emission intensities of the gamma rays from the decay of 224Ra and 212Pb progenies and the half-life of the 212 Pb decay.

Absolute gamma-ray emission intensities for 36 characteristic gamma rays from the decay of 224Ra, 212Pb, and their progeny were determined by measuring sources calibrated for activity by means of primary methods based on well-defined high-purity germanium (HPGe) detectors at both NIST and NPL. Results from the two laboratories agree with recent data evaluations, except for gamma rays with low emission intensities. The decay schemes have been re-balanced based on the new results. In addition, the half-life for 212Pb was measured using several HPGe detectors, ionization chambers, and a well-type NaI(Tl) detector.

Calibration of Traceable Solid Mock (131)I Phantoms Used in an International SPECT Image Quantification Comparison.

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.

Determination of the half-life and the absolute photon emission intensities for the main gamma-ray energies of 124I.

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.

Determination of the internal pair production branching ratio of 90Y.

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 ±â€¯1.5) × 10-6 (k = 1), agrees within 1 standard uncertainty with the recommended value of (32.6 ±â€¯0.7) × 10-6 (k = 1) from the DDEP database.

Standardization of I-124 by three liquid scintillation-based methods.

A solution of 124I was standardized for activity by 4πß(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.

Standardization of (68)Ge/(68)Ga Using Three Liquid Scintillation Counting Based Methods.

A solution containing (68)Ge in equilibrium with its daughter, (68)Ga, has been standardized for the first time at the National Institute of Standards and Technology (NIST) using 3 liquid scintillation-based techniques: live-timed 4πß -γ anticoincidence (LTAC) counting, the Triple-to-Double Coincidence Ratio (TDCR) method, and (3)H-standard efficiency tracing with the CIEMAT(1)/NIST (CNET) method. The LTAC technique is much less dependent on level scheme data and model-dependent parameters and was thus able to provide a reference activity concentration value for the master solution with a combined standard uncertainty of about 0.3 %. The other two methods gave activity concentration values with respective differences from the reference value of +1.2 % and -1.5 %, which were still within the experimental uncertainties. Measurements made on the NIST "4π"γ secondary standard ionization chamber allowed for the determination of calibration factors for that instrument, allowing future calibrations to be made for (68)Ge/(68)Ga without the need for a primary measurement. The ability to produce standardized solutions of (68)Ge presents opportunities for the development of a number of NIST-traceable calibration sources with very low (<1 %) relative standard uncertainties that can be used in diagnostic medical imaging.

Radionuclide calibrator measurements of (18)F in a 3ml plastic syringe.

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.

Standardization of 64Cu activity.

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 4πß(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 ß+/- branching probabilities and a better treatment of ß+/- spectra.

Results of an international comparison of activity measurements of 68Ge.

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 68Ge/68Ga solution. Results for the activity concentration, CA, of 68Ge 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)ß-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)kBqg-1, based on 14 results. The degrees of equivalence and their associated uncertainties are evaluated for each participant. Several participants submitted 3.6mL 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.

Determination of photon emission probability for the main gamma ray and half-life measurements of 64Cu.

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.

Long-term stability of carrier-added (68)Ge standardized solutions.

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.

Development of activity standard for 90 Y microspheres.

(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.

Determination of photon emission probabilities for the main gamma-rays of ²²³Ra in equilibrium with its progeny.

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.

National radioactivity standards for beta-emitting radionuclides used in intravascular brachytherapy.

The uses of beta-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 beta emitters, including 32P, 90Sr/90Y, and 188Re. Additional measurements are made on radionuclidic impurities, half lives, and other decay-scheme parameters (such as branching decay ratios or gamma-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).

A new experimental determination of the dose calibrator setting for 188Re.

UNLABELLED: Accurate activity measurements of radionuclides using commercial dose calibrators requires that the correct dial setting (or calibration factor) be applied. The dose calibrator setting for the medical radionuclide 188Re (as 188ReO4-) has been determined experimentally using solution sources prepared and calibrated at the National Institute of Standards and Technology (NIST). METHODS: The specific activity of two sources (in units of MBq/g) in the standard 5-mL NIST ampoule and in a 5-mL SoloPak dose vial were calibrated using 4pibeta liquid scintillation counting with 3H-standard efficiency tracing and gamma-ray/bremmstrahlung counting in the NIST "4pi" gamma ionization chamber on gravimetrically related sources. RESULTS: The newly determined settings for the NIST Capintec CRC-12 dose calibrator are (631+/-4) x 10 and (621+/-3) x 10 for the respective ampoule and dose vial geometries with an expanded (at a presumed 95% confidence level) uncertainty of 0.4%-0.5% in the activity determination. The setting for the dose vial geometry was independently confirmed using a Capintec CRC-15R at Cedars-Sinai Medical Center using sources calibrated against a NIST standard. CONCLUSION: These new settings result in activity readings 28%-30% lower than those obtained using the previously recommended setting of 496 x 10. This discrepancy most likely results from underestimating the total radiation yield from 188Re decay when calculating the dose calibrator response. This study emphasizes the need for experimental determinations of dose calibrator settings in the geometry in which the measurements will be performed.

Experimental investigation of dose calibrator response for 125I brachytherapy solutions contained in 5 mL plastic syringes and 2 mL conical glass v-vials as a function of filling mass.

The effect of measurement geometry on the determination of the activity of solutions containing 125I 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 x MBq(-1) and 0.231+/-0.004 pA x 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.

Radioassays of yttrium-90 used in nuclear medicine.

Yttrium-90 radioassays are required in nuclear medicine at the gigabecquerel activity level (GBq) for measuring injected activity, and at the becquerel level for measuring individual tissue samples in biodistribution studies. A method of standardizing 90Y for activity using high-efficiency liquid-scintillation counting is described. Solution standards were used to establish the calibration factors for commercial radionuclide calibrators. Detection efficiencies are also presented for liquid-scintillation counting, NaI(T1) bremsstrahlung counting and Cerenkov counting.

The standardization of 62Cu and experimental determinations of dose calibrator settings for generator-produced 62CuPTSM.

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.

Experimental determinations of commercial 'dose calibrator' settings for nuclides used in nuclear medicine.

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 18F, 62Cu, 186Re and 188Re 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.