Study of the biokinetics of zirconium isotopes in humans and its relevance to internal dosimetry [Elektronische Ressource] / Matthias Greiter

Matthias.Greiter

Sujets

• Gesundheit

Informations

• Publié par: technische_universitat_munchen
• Publié le: 01 janvier 2008
• Nombre de lectures: 18
• Langue: Deutsch
• Poids de l'ouvrage: 1 Mo

Extrait

Technische Universität München
Physik-Department


Study of the biokinetics of zirconium isotopes in humans
and its relevance to internal dosimetry


Matthias Greiter


Vollständiger Abdruck der von der Fakultät für Physik
der Technischen Universität München zur Erlangung des akademischen Grades eines
Doktors der Naturwissenschaften
genehmigten Dissertation.

Vorsitzender: Univ.-Prof. Dr. J. L. van Hemmen
Prüfer der Dissertation:
1. Hon.-Prof. Dr. H.G. Paretzke
2. Univ.-Prof. Dr. F. von Feilitzsch

Die Dissertation wurde am 27.09.2007 bei der Technischen Universität München
eingereicht und durch die Fakultät für Physik am 22.04.2008 angenommen.

i




























Author contact information:

Matthias Greiter
Institute of Radiation Protection
Helmholtz Zentrum München
German Research Center for Environmental Health (GmbH)
Ingolstaedter Landstrasse 1
85764 Neuherberg
Germany
E-mail: [e-mail]

ii
Table of contents


Abstract ...................................................................................................................................... 1
List of acronyms, symbols and abbreviations ............................................................................ 2
1 Aim of the study......................................................................................................... 3
1.1 Natural occurrence of zirconium compounds ............................................................ 3
1.2 Applications of stable zirconium................................................................................ 5
1.3 Applications of unstable isotopes of zirconium ......................................................... 5
1.4 Current biokinetic model of the International Commission on Radiological
Protection (ICRP)....................................................................................................... 7
2 Investigations with stable isotope tracers................................................................. 11
2.1 Double isotope technique and obtainable data 11
2.2 Preparation of tracer solutions.................................................................................. 12
2.3 Experimental scheme...............................................................................................14
3 Measurement methods.............................................................................................16
3.1 Requirements............................................................................................................
3.2 Mass spectrometric methods .................................................................................... 16
3.2.1 Sample preparation for thermal ionisation mass spectrometry (TIMS)........... 21
3.2.2 Description of the TIMS instrument and measurement ................................... 24
3.2.3 Tracer concentration calculation with the isotope dilution technique.............. 26
3.3 Activation analysis...................................................................................................28
3.3.1 Proton nuclear activation (PNA) sample preparation ...................................... 31
3.3.2 PNA instrumental setup and experimental conditions ..................................... 32
3.3.3 PNA tracer concentration calculation .............................................................. 34
4 Errors and uncertainty.............................................................................................. 38
4.1 Tracers and samples.................................................................................................40
4.2 TIMS........................................................................................................................ 41
4.3 PNA.......................................................................................................................... 42
5 Model development..................................................................................................44
5.1 Fractional absorption................................................................................................
5.1.1 Double tracer technique ................................................................................... 45
5.1.2 Convolution integral technique........................................................................46
5.2 First-order kinetic compartment models .................................................................. 47
5.2.1 Theoretical a priori identifiability .................................................................... 48
5.2.2 Model development process............................................................................. 49
5.3 Dosimetry.................................................................................................................53
6 Results and discussion.............................................................................................57
6.1 Investigations...........................................................................................................57
6.2 Sample measurements and method comparison....................................................... 58
6.2.1 TIMS and PNA detection limits....................................................................... 58
6.2.2 Combined uncertainty......................................................................................61
iii6.2.3 Correlation of TIMS and PNA results.............................................................. 62
6.2.4 Measured data..................................................................................................65
6.3 Model development69
6.3.1 Fractional absorption without compartment models........................................
6.3.2 Tracer kinetics and compartment model structure ........................................... 72
6.3.3 Proposed new model........................................................................................81
6.4 Dosimetry.................................................................................................................89
6.4.1 Reproducibility of ICRP ingestion dose coefficients....................................... 89
6.4.2 Influence of daughter radionuclide modelling on dose coefficients ................ 90
6.4.3 Gender differences due to SEE values ............................................................. 91
6.4.4 Differences due to alimentary tract models...................................................... 92
956.4.5 Dose coefficients of Zr for the proposed new zirconium biokinetic model .. 93
6.4.6 Gender differences resulting from the use of the HAT model......................... 93
6.4.7 Effect of fractional absorption on ingestion dose coefficients 95
6.4.8 Contribution of individual target tissues to effective dose............................... 96
6.4.9 Summary of dosimetry................................................................................... 100
7 Conclusions............................................................................................................101
Acknowledgements ................................................................................................................ 103
Bibliography........................................................................................................................... 105
Annex ..........................................................................................................................................I
A. TIMS method development.........................................................................................I
B. Algorithm for the calculation of absorption rates ....................................................VI

ivAbstract

Internal radiation dosimetry relies on biokinetic models linking exposure and dose, since
internal dose cannot be measured readily in exposed persons. The structure and parameters of
these models are usually estimated from animal and, if available, human study data.
The purpose of the present work is to extend the limited knowledge about the element
zirconium. Data on zirconium metabolism, especially fractional absorption, retention in the
body and excretion, are obtained directly from humans by the use of enriched stable
zirconium isotopes as tracers. Thermal ionisation mass spectrometry (TIMS) and proton
nuclear activation (PNA) are optimised for the measurement of nanogram amounts of tracer
zirconium in biological samples. Both methods are evaluated with respect to detection limit,
uncertainty and practical applicability.
Blood plasma and urinary data from nine double tracer studies with up to 100 d duration serve
as input for developing a new first order kinetic compartment model. The new model is based
on the current zirconium model proposed by the International Commission on Radiological
Protection (ICRP).
95Ingestion dose coefficients for Zr are presented for the new model. Depending on gender
and the chemical form of the ingested zirconiu