EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations

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Abstract

A framework is proposed for modelling the uncertainty in the measurement processes constituting the dosimetry chain that are involved in internal absorbed dose calculations. The starting point is the basic model for absorbed dose in a site of interest as the product of the cumulated activity and a dose factor. In turn, the cumulated activity is given by the area under a time–activity curve derived from a time sequence of activity values. Each activity value is obtained in terms of a count rate, a calibration factor and a recovery coefficient (a correction for partial volume effects). The method to determine the recovery coefficient and the dose factor, both of which are dependent on the size of the volume of interest (VOI), are described. Consideration is given to propagating estimates of the quantities concerned and their associated uncertainties through the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and its associated uncertainty. This approach is demonstrated in a clinical example.

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Most cited references 23

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MIRD pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry--standardization of nomenclature.

Wesley Bolch, Keith Eckerman, George Sgouros … (2009)

The internal dosimetry schema of the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine has provided a broad framework for assessment of the absorbed dose to whole organs, tissue subregions, voxelized tissue structures, and individual cellular compartments for use in both diagnostic and therapeutic nuclear medicine. The schema was originally published in 1968, revised in 1976, and republished in didactic form with comprehensive examples as the MIRD primer in 1988 and 1991. The International Commission on Radiological Protection (ICRP) is an organization that also supplies dosimetric models and technical data, for use in providing recommendations for limits on ionizing radiation exposure to workers and members of the general public. The ICRP has developed a dosimetry schema similar to that of the MIRD Committee but has used different terminology and symbols for fundamental quantities such as the absorbed fraction, specific absorbed fraction, and various dose coefficients. The MIRD Committee objectives for this pamphlet are 3-fold: to restate its schema for assessment of absorbed dose in a manner consistent with the needs of both the nuclear medicine and the radiation protection communities, with the goal of standardizing nomenclature; to formally adopt the dosimetry quantities equivalent dose and effective dose for use in comparative evaluations of potential risks of radiation-induced stochastic effects to patients after nuclear medicine procedures; and to discuss the need to identify dosimetry quantities based on absorbed dose that address deterministic effects relevant to targeted radionuclide therapy.

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MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates.

M Stabin, Gareth Howell, Steven J. Siegel … (1999)

This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examples and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories. The measurement of the biodistribution of radiopharmaceuticals is an important aspect in calculating absorbed dose from internally deposited radionuclides. Three phases are presented: data collection, data analysis and data processing. In the first phase, data collection, the identification of source regions, the determination of their appropriate temporal sampling and the acquisition of data are discussed. In the second phase, quantitative measurement techniques involving imaging by planar scintillation camera, SPECT and PET for the calculation of activity in source regions as a function of time are discussed. In addition, nonimaging measurement techniques, including external radiation monitoring, tissue-sample counting (blood and biopsy) and excreta counting are also considered. The third phase, data processing, involves curve-fitting techniques to integrate the source time-activity curves (determining the area under these curves). For some applications, compartmental modeling procedures may be used. Last, appendices are included that provide a table of symbols and definitions, a checklist for study protocol design, example formats for quantitative imaging protocols, temporal sampling error analysis techniques and selected calculational examples. The utilization of the presented approach should aid in the standardization of protocol design for collecting kinetic data and in the calculation of absorbed dose estimates.

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Choosing the optimal fit function: comparison of the Akaike information criterion and the F-test.

S Reske, Michael Hohl, Peter Kletting … (2007)

In many circumstances of data fitting one has to choose the optimal fitting function or model among several alternatives. Criteria or tests on which this decision is based are necessary and have to be well selected. In this preliminary analysis the application of the corrected Akaike information criterion is demonstrated considering the example of determining pharmacokinetic parameters for the blood serum time activity curves of 111In-labeled anti-CD66 antibody. Another model selection criterion, the F-test, is used for comparison. For the investigated data the corrected Akaike information criterion has proved to be an effective and efficient approach, applicable to nested and non-nested models.

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Author and article information

Contributors

Jonathan I. Gear: jgear@icr.ac.uk , jonathan.gear@icr.ac.uk

Journal

Journal ID (nlm-ta): Eur J Nucl Med Mol Imaging

Journal ID (iso-abbrev): Eur. J. Nucl. Med. Mol. Imaging

Title: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1619-7070

ISSN (Electronic): 1619-7089

Publication date (Electronic): 14 September 2018

Publication date PMC-release: 14 September 2018

Publication date (Print): 2018

Volume: 45

Issue: 13

Pages: 2456-2474

Affiliations

[1 ]The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, Downs Road, Sutton, SM2 5PT UK

[2 ]ISNI 0000 0000 8991 6349, GRID grid.410351.2, National Physical Laboratory, ; Teddington, TW11 0LW UK

[3 ]ISNI 0000 0001 0930 2361, GRID grid.4514.4, Department of Medical Radiation Physics, Clinical Sciences Lund, , Lund University, ; Lund, Sweden

[4 ]ISNI 0000 0004 1936 9748, GRID grid.6582.9, Medical Radiation Physics, Department of Nuclear Medicine, , Ulm University, ; Ulm, Germany

[5 ]ISNI 000000040459992X, GRID grid.5645.2, Nuclear Medicine, , Erasmus MC, ; Rotterdam, The Netherlands

Article

Publisher ID: 4136

DOI: 10.1007/s00259-018-4136-7

PMC ID: 6208822

PubMed ID: 30218316

SO-VID: 2a0b1cc9-397a-4af5-9420-841fa331f82f

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 9 August 2018

Date accepted : 14 August 2018

Custom metadata

ScienceOpen disciplines: Radiology & Imaging

Keywords: dosimetry,uncertainty analysis

Data availability:

ScienceOpen disciplines: Radiology & Imaging

Keywords: dosimetry, uncertainty analysis

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