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. 2023 Jan;415(2):255-268.
doi: 10.1007/s00216-022-04311-0. Epub 2022 Sep 22.

Enriched stable 204Pb as tracer at ultra-low levels in clinical investigations

Johanna Irrgeher  1 , Thomas Berger  2 , Anastassiya Tchaikovsky  2 , Cornelius Tschegg  2 , Ghazaleh Gouya  3 , Peter Lechner  4 , Anika Retzmann  5 , Christine Opper  5   6 , Christa Firbas  7 , Michael Freissmuth  8 , Kerstin Peschel-Credner  3 , Karolina Anderle  8 , Claudia Meisslitzer  2 , Michael Wolzt  7 , Thomas Prohaska  5
Affiliations

Enriched stable 204Pb as tracer at ultra-low levels in clinical investigations

Johanna Irrgeher et al. Anal Bioanal Chem. 2023 Jan.

Abstract

The potential of enriched Pb (204Pb) was assessed to monitor pathways of trace levels of Pb in the pg range within the human body via isotope pattern variation in situations where natural lead cannot be used as a tracer due to regulatory limitations. Isotope ratio measurements were accomplished by means of (multi-collector) inductively coupled plasma mass spectrometry including a comparison of single and multi-collector ICP-MS for low-level 204Pb assessment. Isotopic pattern results from a blend of a large quantity of the element with a natural isotopic composition and an enriched stable isotope at orders of magnitude lower levels pose a nontrivial analytical problem. Isotope pattern deconvolution was successfully applied as mathematical tool based on multiple linear regressions. The method allowed for deconvolving the isotope pattern from measured isotope ratios without knowing the quantities of different isotope sources incorporated and mixed into the sample at levels of < 1 pg 204Pb/g blood. The objective of this manuscript is to evaluate and summarize the analytical aspects for Pb isotope pattern deconvolution based on the results of a clinical trial, where a 204Pb-enriched isotope tracer was applied to investigate the bioavailability of orally applied Pb along with purified clinoptilolite tuff as potential supplement. This unique approach allows to reduce tracer amounts to harmless levels to human health, which are in accordance with the legal regulative to study enrichment levels of < 0.01% in human blood.

Keywords: Blood; Clinoptilolite; ICP-MS; Isotope pattern deconvolution; Lead; Zeolite.

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Conflict of interest statement

The funder had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Financial interests: JI, AR, CO and TP have fully been employed by Montanuniversität Leoben (MUL). MUL has received research funding from Glock Health Science and Research GmbH in the double-blinded study. JI, AR, CO and TP declare no financial interests.

Non-financial interests: JI, AR, CO and TP declare no non-financial interests.

Financial interests: TB, AT, CT and CM have fully been employed by the funder Glock Health Science and Research GmbH. The funder had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Non-financial interests: The authors declare no non-financial interests.

Financial interests: MF, MW and KA were fully employed by the Center of Physiology and Pharmacology, Medical University of Vienna, which received research funding by Glock Health Science and Research GmbH.

Non-financial interests: MF was on the board of scientific advisors of the Gaston H. Glock Research Laboratories for Exploratory Drug Development at the time the study was carried out. KA and MW declare no non-financial interests.

Financial interests: CF was fully funded by the Department of Clinical Pharmacology, Medical University of Vienna. In her role, she was responsible for the clinical trial. CF declares no financial interests.

Non-financial interests: CF declares no non-financial interests.

Financial interests: GG and PL are self-employed with Gouya Insights and LGS-INSIGHTS, respectively, and were responsible for coordination, planning and statistical evaluation of the study. Both companies received research funding from Glock Health Science and Research GmbH.

Non-financial interests: The authors declare no non-financial interests.

Financial interests: KPC has been fully employed at Gouya Insights. She declares no financial interest.

Non-financial interests: KPC declares no non-financial interests.

Figures

Fig. 1
Fig. 1
Molar fraction of 204Pb tracer calculated by IPD vs. measured 208Pb/204Pb ratio. The theoretical enrichment levels from experimental design are compared to the actual measured enrichment levels assessed from spiking experiments using BCR-636 spiked with increasing amounts of 204Pb tracer solution
Fig. 2
Fig. 2
a (left) Molar fraction of 204Pb tracer by IPD of subject-01 vs sampling time after administration of tracer; error bars represent 1SD of the measurement. b (right) Molar fraction of 204Pb tracer normalized for HCT/BMI by IPD of subject-01 vs sampling time; error bars represent combined uncertainties u (k = 1) of the normalized molar fraction
Fig. 3
Fig. 3
a (left) Molar fraction of 204Pb tracer by IPD of subject-02 vs sampling time after administration of tracer; error bars represent 1SD of the measurement. b (right) Molar fraction of 204Pb tracer normalized for HCT/BMI by IPD of subject-02 vs sampling time; error bars represent combined uncertainties u (k = 1) of the normalized molar fraction
Fig. 4
Fig. 4
The maximum enrichment as 204Pb-molar fraction in Pb normalized to HCT/BMI of all 42 subjects from the three treatment groups (placebo, 1 × 2.0 g G-PUR and 2 × 2.0 g G-PUR) (independent of the time of maximum enrichment in tracer) sorted by enrichment, error bars correspond to u = 10% (k = 1)
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