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Nuklearmedizin 2018; 57(06): 224-233
DOI: 10.3413/Nukmed-0999-18-09
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Normal Values of Renal Function measured with 99mTechnetium Mercaptoacetyltriglycine SPECT in Mice with Respect to Age, Sex and Circadian Rhythm

Normwerte für die Nieren-SPECT mit 99mTechnetium Mercaptoacetyltriglycin bei der Maus in Abhängigkeit von Alter, Geschlecht und circadianem Rhythmus
Kai Huang
1   Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Germany
,
Mathias Lukas
1   Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Germany
,
Ingo G. Steffen
1   Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Germany
,
Catharina Lange
1   Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Germany
,
Eleonore L. Huang
1   Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Germany
,
Viktoria Dorau
1   Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Germany
2   Department of Internal Medicine, Military Hospital Hamburg, Germany
,
Winfried Brenner
1   Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Germany
,
Nicola Beindorff
3   Berlin Experimental Radionuclide Imaging Center (BERIC), Charité – Universitätsmedizin
› Author AffiliationsThis work was supported in part by the Technologiestiftung Berlin (TSB) for SPECT/CT use. This manuscript is based in parts on the results of the doctoral thesis of Kai Huang.
Further Information

Publication History

received: 10 September 2018

accepted: 02 November 2018

Publication Date:
18 December 2018 (online)

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Summary

Aim: The aim of this study is to present normal values for 99mtechnetium mercaptoacetyltriglycine renal uptake kinetics as a function of age, sex and circadian rhythm in mice using multi-pinhole SPECT.

Methods: Dynamic multi-pinhole SPECT semistationary acquisitions consisting of 10 20 s frames followed by 25 50 s frames began prior to intravenous injection of 50 MBq in 12 female (F) and 12 male (M) C57BL/6N mice. Each mouse had follow-up imaging at 1, 3, 6, 12 and 22 months of age. To assess physiological changes related to circadian rhythm, animals were imaged during light (sleeping phase, SP) and dark conditions (awake phase, AP). Renal excretion time activity curves were analysed to determine maximum time to peak uptake (Tmax).

Results: There was an age-related effect on renal Tmax. In one-month-old mice median Tmax (1.8 min) occurred later than in 3-month-old mice (1.7 min; p = 0.035). Thereafter, mice showed continuously increasing time to renal Tmax up to an age of 22 months (2.3 min; p < 0.001). Female mice showed a significantly later renal Tmax than males (F 2.1 min, M 1.7 min; p < 0.001) from 3 months onwards. An effect of circadian rhythm on renal uptake was also observed with borderline relevance. Pooled results for all animals showed that renal Tmax appeared at a later timepoint after injection during SP (2.0 min) than during AP (1.8 min; p = 0.019), while in age and sex matched animal groups no significant differences were observed.

Conclusion: This study showed that kidney function in mice is dependent on age and sex, whereas circadian rhythm does not cause a significant effect. Therefore, age and sex should be considered as important study design considerations for renal scintigraphy in mice, while the impact of circadian rhythm seems negligible.

Zusammenfassung

Ziel: Ziel dieser Studie war die Erhebung von Normwerten für die Nieren-Uptake-Kinetik von 99mTechnetium-Mercaptoacetyltriglycin Multipinhole SPECT in Abhängigkeit von Alter, Geschlecht und circadianem Rhythmus bei der Maus.

Methoden: Bei 12 weiblichen (F) und 12 männlichen (M) C57BL/6N Mäusen wurden unmittelbar vor intravenöser Injektion von 50 MBq 99mTc-MAG3 dynamische semistationäre Multipinhole-SPECT-Akquisitionen von 10 Frames à 20 s gefolgt von 25 Frames à 50 s gestartet. Jede Maus wurde im Altersverlauf mit 1, 3, 6, 12 und 22 Monaten untersucht. Um physiologische Veränderungen bezüglich des circadianen Rhythmus zu erfassen, wurden die Tiere während der Hellphase (Schlafphase, SP) sowie der Dunkelphase (Wachphase, AP) untersucht. Die Nierenfunktion ist als Zeit-Aktivitäts-Kurve dargestellt und die Zeit bis zum Maximum (Tmax) als Median in Minuten aufgeführt.

Ergebnisse: Generell zeigte sich ein altersabhängiger Einfluss auf Tmax. Bei 1 Mo alten Tieren erfolgte Tmax (1,8 min) später als mit 3 Mo (1,7 min; p = 0,035). Im weiteren Altersverlauf zeigten die Mäuse einen kontinuierlich späteren Zeitpunkt von Tmax bis 22 Mo (2,3 min; p < 0,001). Weibchen zeigten ein signifikant späteres Tmax als Männchen (F = 2,1 min, M = 1,7 min; p < 0,001) ab einem Alter von 3 Monaten. Für den circadianen Rhythmus wurde ein nicht eindeutiger Effekt beobachtet. Wenn alle Tiere zusammengefasst wurden, erfolgte Tmax während der SP (2,0 min) später als während der AP (1,8 min; p = 0,019) während sich in den alters- und geschlechtsgetrennten Gruppen keine signifikanten Unterschiede nachweisen ließen.

Schlussfolgerung: Diese Studie zeigte einen deutlichen Einfluss von Alter und Geschlecht auf die Nierenfunktion bei der Maus während der circadiane Rhythmus keinen eindeutigen Effekt aufwies. Deshalb sollten bei Nierenstudien mit Mäusen die Faktoren Alter und Geschlecht berücksichtigt werden, während der circadiane Rhythmus vernachlässigbar erscheint.

Keywords

Renal function - 99mTc-MAG3 - SPECT - age - sex - circadian rhythm - mouse

Schlüsselwörter

Nierenfunktion - 99mTc-MAG3 - SPECT - Alter - Geschlecht - circadianer Rhythmus - Maus
 

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