National Radioactivity Standards for β-Emitting Radionuclides Used in Intravascular Brachytherapy

doi:10.1016/S0360-3016(98)00012-1

International Journal of Radiation OncologyBiologyPhysics

Volume 41, Issue 1, 1 April 1998, Pages 207-216

https://doi.org/10.1016/S0360-3016(98)00012-1 Get rights and content

Abstract

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 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 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).

Section snippets

Applications and the Need for Standards

Therapeutic nuclear medicine has seen rapid growth in the past few years in several areas: radioimmunotherapy, bone palliation, bone marrow ablation, and radionuclidic synovectomy. The resurgence of interest in what are often called “magic bullets” is a result of improvements in tissue-specific agents, such as monoclonal antibodies, and organ-specific pharmaceuticals, such as bone-seeking diphosphonates. The nuclides under consideration are mainly short-lived, high-energy β emitters 1, 2.

All of

The Role of NIST

The National Institute of Standards and Technology, formerly the National Bureau of Standards, was created by a Congressional act in 1901 to be the source and custodian of standards for physical measurements in the United States. As a part of its mandate, the responsibilities and goals of NIST are to develop and maintain national reference standards and definitive methods of analysis; to certify and issue suitable transfer standards; and to provide mechanisms that assure the quality of

Radionuclidic Standardization of β Emitters

Standardizations of β-emitting radionuclides by 4πβ liquid scintillation (LS) spectrometry are routinely performed by NIST using the Centro de Investigaciones Energeticas, Medioambientales y Technologicas (CIEMAT)/NIST method for efficiency tracing. This protocol 11, 12, originated by the CIEMAT and NIST, is one of the more commonly invoked methodologies for LS spectrometry efficiency tracing. The method uses various updated and revised versions of the CIEMAT-developed EFFY code 13, 14 to

Examples of Recent NIST Standardization Activities: ⁹⁰Y, ³²P, and ¹⁸⁸Re

Following are three examples that illustrate the methods used to standardize high-energy β emitters at the NIST, and the use of these standardized solutions to characterize radionuclide calibrators for use in radioassays prior to therapeutic administration.

Conclusions

High-energy β-particle emitters, which are being widely used in therapeutic nuclear medicine and are being evaluated for use in intravascular brachytherapy, may be accurately standardized by high-efficiency liquid-scintillation counting. Solutions standardized by this technique may then be used to establish the counting efficiencies for various practical sample geometries for dose calibrators and NaI(Tl) γ counters. These very practical instruments are exceedingly useful for relative

Acknowledgements

The authors express thanks to F. F. (Russ) Knapp, Jr., and Saed Mirzadeh at the Oak Ridge National Laboratory for supplying ¹⁸⁸Re; Sam Lott at NeoCardia for providing ³²P sources; and Mary Anne Dell at Capintec for discussions on dose calibrators. They also thank their colleagues F. J. Schima, D. D. Hoppes, and M. P. Unterweger, the physicists at NIST who measure and evaluate nuclear decay scheme data for these radionuclides.

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Cited by (14)

The measurement of activity contained in a 32P stainless-steel stent by destructive assay
2002, Applied Radiation and Isotopes
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%.
Activity characterization of pure-β-emitting brachytherapy sources
2002, Applied Radiation and Isotopes
A generalized approach for characterizing the activity content of sealed β-emitting sources has been developed, and was employed to establish National Institute of Standards and Technology based activity standardizations for three different types of intravascular brachytherapy sources. Initial ionization current measurements on the sources prior to destructive assays led to the establishment of calibration factors that can be used for subsequent non-destructive measurements of similar sources. Activity characterizations are needed to unequivocally relate theoretic absorbed-dose modeling results to dosimetric measurements, as well as to establish production and quality controls by the source manufacturers, and to satisfy the requirements of various governmental regulatory authorities.
Calibration of 32P 'hot-wall' angioplasty-balloon-catheter sources by liquid-scintillation-spectrometry-based destructive radionuclidic assays
2001, Applied Radiation and Isotopes
A very quantitative, destructive-analysis procedure was devised for assaying the ³²P activity content of “hot-wall” angioplasty-balloon catheters. These sources, developed and under investigation by Radiance Medical Systems, Inc. (Irvine, CA), are intended for use in the prophylactic inhibition of restenosis following balloon angioplasty in heart-disease patients. The assay was based on performing a physicochemical digestion of the balloon catheter to extract the ³²P activity followed by liquid-scintillation (LS) spectrometry of the resultant solutions. Measurement-based corrections were applied for the residual activity remaining in the digested balloon debris and in all of the digestion apparatus. The LS spectrometry, with ³H-standard efficiency tracing, utilized a previously-developed method for resolving the always-present ³³P impurity. Initial ionization current measurements on the sources prior to the destructive assays led to the establishment of calibration factors that can be used for subsequent non-destructive radionuclidic measurements on similar balloon-catheter sources.
Needs for radioactivity standards and measurements in the life sciences
2000, Applied Radiation and Isotopes
For almost 100 years, radioactivity has been one of the major tools in medicine. Therapeutic applications that began with ²²⁶Ra and ²²²Rn implants have rapidly grown to include about 20 radionuclides with radiations specifically chosen to treat at different depths in tissue — ranging from a few millimeters for intravascular therapy to a few centimeters in the case of large solid tumors. Systemic treatments with radiopharmaceuticals have grown from the traditional ¹³¹I to more than ten candidate nuclides which are to be labeled to tumor-specific radiopharmaceuticals. Diagnostic radiopharmaceuticals are used in over 13 million procedures in the United States annually. About 40 nuclides are under investigation for these applications including single photon emitters for SPECT (single photon emission computed tomography) and positron emitters for PET (positron emission tomography). In addition to the mainstays of therapeutic and diagnostic radiology, radionuclides are widely used for in vitro tracers in the life sciences and represent one of the main tools in the field of molecular biology.
On the radioanalytical methods used to assay stainless-steel- encapsulated, ceramic-based 90Sr-90Y intravascular brachytherapy sources
2000, Applied Radiation and Isotopes
Very quantitative radiochemical procedures for the destructive assay of stainless-steel-encapsulated, ceramic-based ⁹⁰Sr–⁹⁰Y intravascular brachytherapy sources (termed ‘seeds’) have been devised. These seeds, developed and provided by Bebig Isotopentechnic und Umweltdiagnostik (Berlin, Germany) in collaboration with the Novoste Corporation (Norcross, GA), are intended for use in the prophylactic treatment of restenosis following balloon angioplasty in heart-disease patients. The procedures were applied to the radionuclidic assay of both the bare-ceramic source materials (of proprietary composition) contained within the seeds and to the stainless-steel (SS) sealed sources. The approach consisted of extracting some arbitrary fraction of the ⁹⁰Sr activity from the ceramic-like material and assaying the resulting solution by 4πβ liquid scintillation (LS) spectrometry with ³H-standard efficiency tracing. The fraction of extracted activity was determined by ionization current measurements before and after the chemical extraction. All of the ionization current and LS-based activity determinations were made under the experimentally-verified conditional that ⁹⁰Y was in radioactive equilibrium with ⁹⁰Sr. For the assay of the SS-jacketed seeds, the encapsulation was initially dissolved and the resultant solution was also assayed by LS spectrometry to determine the amount of activity removed by the SS dissolution step. The developed protocol included provisions for accounting for all possible losses of ⁹⁰Sr activity in the chemical and source-handling procedures, for the unrecovered activity in the extracted source material and for any residual activity in the solution-transfer and source-handling tools. These destructive assays were required for relating radiochromic-film measurements of the absorbed dose spatial distributions for the seeds to theoretic dose modelling and for establishing calibration factors for subsequent non-destructive radionuclidic measurements on the seeds.
Dosimetry calculation for a novel PHOSPHORUS-32- impregnated balloon angioplasty catheter for intravascular brachytherapy
1999, Cardiovascular Radiation Medicine
Purpose. A phosphorus-32-impregnated balloon angioplasty catheter was used in a novel technique of simultaneous angioplasty and vessel irradiation. The ³²P radionuclides were distributed on the surface of the balloon so that a certain amount of radiation was delivered while angioplasty was performed. Three-dimensional dosimetry and dose–time relationship needs to be established for the catheter so that quantitative dosimetric information is available for both clinical treatment and research investigation.
Methods and Materials. The ³²P-impregnated balloon of an angioplasty catheter was assumed to have a cylindrical shape, and the radionuclides were assumed to be distributed uniformly on the curved surface of the cylinder. The dose rate at a point in space was computed by integrating the point dose-rate kernel of ³²P over the radioactive surface of the balloon. The point dose-rate kernel was computed with Monte Carlo simulation of radiation transport. The energy spectra of ³²P based on a mathematical model was used in the calculations. The three-dimensional dose distributions and dose–time relationships were calculated for balloons of various lengths and radii.
Results. At a short radial distance (e.g., 0.2 mm) away from the balloon surface, the dose distribution was uniform across a large portion of the balloon along the longitudinal axis, and dropped off rapidly at both ends of the balloon. Uniformity became worse as the radial distance increased. Uniformity was almost independent of balloon radius. The underdosed length at each end of the balloon was also almost independent of balloon length. In the central transverse plane, the dose reached a maximum at the surface of the balloon and then dropped off rapidly as the distance increases. Relative dose coverage outside the balloon was approximately independent of balloon radius and length, and the absolute dose coverage was approximately inversely proportional to balloon radius and length, assuming same total activity.
Conclusions. Point dose-rate kernel of ³²P beta emitter and the three-dimensional dose distributions of a ³²P-impregnated balloon from an novel angioplasty catheter were calculated. A rule of thumb for dose calculation and dose coverage was established for simultaneous angioplasty and vascular brachytherapy with a ³²P-impregnated balloon catheter.

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¹: Presented at the symposium on Advances in Cardiovascular Radiation Therapy, Washington, DC, 20–21 February 1997.

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International Journal of Radiation OncologyBiologyPhysics

Abstract

Section snippets

Applications and the Need for Standards

The Role of NIST

Radionuclidic Standardization of β Emitters

Examples of Recent NIST Standardization Activities: ⁹⁰Y, ³²P, and ¹⁸⁸Re

Conclusions

Acknowledgements

References (25)

Radiobiologic Implications of the microscopic distribution of energy from radionuclides

Nucl. Med. Biol.

Needs for brachytherapy source calibrations in the United States

Nucl. Instrum. Meth. A

Calibration of the NPL secondary standard radionuclide calibrator for ³²P, ⁸⁹Sr, and ⁹⁰Y

Nucl. Instrum. Meth. A.

Standardization of carbon-14 by 4πβ liquid-scintillation efficiency tracing with hydrogen-3

Int. J. Appl. Radiat. Isotopes

EFFYA new program to calculate the counting efficiency of beta particles in liquid scintillation

Comput. Phys. Commun.

Liquid scintillation counting efficiency as a function of the figure of merit for pure beta-particle emitters

Int. J. Appl. Radiat. Isot.

New and revised half-life measurement results

Nucl. Instrum. Meth.

Determination of the photon emission rates of the NBS Long-Lived Mixed-Radionuclide Standard

Nucl. Instrum. Meth.

Chemistry for commercial scale production of yttrium-90 for medical research

Appl. Radiat. Isot.

Radioassays of yttrium-90 for use in nuclear medicine

Nucl. Med. Biol.

Therapeutic radionuclidesProduction and decay property considerations

J. Nucl. Med.

Cited by (14)

The measurement of activity contained in a <sup>32</sup>P stainless-steel stent by destructive assay

Activity characterization of pure-β-emitting brachytherapy sources

Calibration of <sup>32</sup>P 'hot-wall' angioplasty-balloon-catheter sources by liquid-scintillation-spectrometry-based destructive radionuclidic assays

Needs for radioactivity standards and measurements in the life sciences

On the radioanalytical methods used to assay stainless-steel- encapsulated, ceramic-based <sup>90</sup>Sr-<sup>90</sup>Y intravascular brachytherapy sources

Dosimetry calculation for a novel PHOSPHORUS-32- impregnated balloon angioplasty catheter for intravascular brachytherapy

Physics ContributionsNational Radioactivity Standards for β-Emitting Radionuclides Used in Intravascular Brachytherapy 1

Abstract

Section snippets

Applications and the Need for Standards

The Role of NIST

Radionuclidic Standardization of β Emitters

Examples of Recent NIST Standardization Activities: 90Y, 32P, and 188Re

Conclusions

Acknowledgements

Nucl. Med. Biol.

Nucl. Instrum. Meth. A

Nucl. Instrum. Meth. A.

Int. J. Appl. Radiat. Isotopes

Comput. Phys. Commun.

Int. J. Appl. Radiat. Isot.

Nucl. Instrum. Meth.

Nucl. Instrum. Meth.

Appl. Radiat. Isot.

Nucl. Med. Biol.

Therapeutic radionuclidesProduction and decay property considerations

J. Nucl. Med.

Physics Contributions
National Radioactivity Standards for β-Emitting Radionuclides Used in Intravascular Brachytherapy ¹

Examples of Recent NIST Standardization Activities: ⁹⁰Y, ³²P, and ¹⁸⁸Re