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Nuklearmedizin 2012; 51(05): 170-178
DOI: 10.3413/Nukmed-0506-12-05
Original article
Schattauer GmbH

Sodium-iodide symporter positive cells after intracellular uptake of 99mTc versus α-emitter 211At

Reduction of clonogenic survival and characterization of DNA damageNatrium-Iodid-Symporter-positive Zellen nach intrazellulärer Aufnahme von 99mTc im Vergleich zum α-Emitter 211AtReduktion des klonogenen Überlebens und Charakterisierung von DNA-Schäden
J. Kotzerke
1   Department of Nuclear Medicine, University Hospital, Carl Gustav Carus, Technische Universität Dresden, Germany
,
M. Wendisch
1   Department of Nuclear Medicine, University Hospital, Carl Gustav Carus, Technische Universität Dresden, Germany
,
R. Freudenberg
1   Department of Nuclear Medicine, University Hospital, Carl Gustav Carus, Technische Universität Dresden, Germany
,
R. Runge
1   Department of Nuclear Medicine, University Hospital, Carl Gustav Carus, Technische Universität Dresden, Germany
,
L. Oehme
1   Department of Nuclear Medicine, University Hospital, Carl Gustav Carus, Technische Universität Dresden, Germany
,
G.J. Meyer
2   Department of Nuclear Medicine, Centre for Radiology, Hannover Medical School, Hannover, Germany
,
L. A. Kunz-Schughart
3   OncoRay – National Center for Radiation Research in Oncology, Carl Gustav Carus, Technische Universität Dresden, Germany
,
G. Wunderlich
1   Department of Nuclear Medicine, University Hospital, Carl Gustav Carus, Technische Universität Dresden, Germany
› Institutsangaben
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Publikationsverlauf

received: 31. Mai 2012

accepted in revised form: 30. August 2012

Publikationsdatum:
02. Januar 2018 (online)

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Summary

Purpose: We evaluated the DNA damaging potential of Auger electrons emitted in the decay of 99mTc compared to α-particles of 211At. Material and methods: The impact of 99mTc and 211At was monitored in a NIS-expressing rat thyroid cell model PC Cl3 with varying, yet defined intra- and extracellular radionuclide distribution (using ± perchlorate). The radiotoxicity of 99mTc and 211At was studied by the comet assay under neutral and alkaline conditions and colony formation. Results: In the presence of perchlorate, the radioactivity yielding 37 % cellular survival, A37, was estimated to be (0.27 ± 0.02) MBq/ml and (450 ± 30) MBq/ml for 211At and 99mTc, respectively. In absence of perchlorate, cellular radiotracer uptake was similar for both radionuclides (2.2 %, 2.7 %), yet the A37 was reduced by 82% for the α-emitter and by 95 % for 99mTc. Cellular dose increased by a factor of 5 (211At) and 38 (99mTc). Comet assays revealed an increased DNA damage after intracellular uptake of both radiotracers. Conclusions: The data indicate damage to the cell to occur from absorbed dose without recognizable contribution from intracellular heterogeneity of radionuclide distribution. Comet assay under alkaline and neutral conditions did not reveal any shift to more complex DNA damage after radionuclide uptake. Cellular uptake of 99mTc and 211At increased cellular dose and reduced clonogenic survival.

Zusammenfassung

Ziel: Untersucht wurden der Auger-Elektronen- Emitter 99mTc im Vergleich mit dem α-Emitter 211At hinsichtlich des Potentials zur DNA-Schädigung. Material und Methode: An NIS-positiven PC Cl3-Zellen wurde die Wirkung von 99mTc und 211At bei variabler intra- und extrazellulärer Radionuklidverteilung (An- und Abwesenheit von Perchlorat) überprüft. Die Radiotoxizität beider Nuklide wurde mittels alkalischen und neutralen Komet-Assay sowie Koloniebildungsassay bestimmt. Ergebnisse: In Anwesenheit von Perchlorat betrug die Aktivität A37, welche zu 37%igem Zellüberleben führt, (0,27 ± 0,02) MBq/ml für 211At und (450 ± 30) MBq/ ml für 99mTc. Bei Abwesenheit von Perchlorat wurde ein vergleichbarer Uptake für beide Nuklide beobachtet (2,2 % bzw. 2,7 %), wobei A37 für den α-Emitter um 82 % sank und um 95 % für 99mTc. Dabei erhöhte sich die Zelldosis um den Faktor 5 (211At) bzw. 38 (99mTc). Für beide Radiotracer wurde ein Anstieg der DNA-Schädigung mittels Komet-Assay beobachtet. Schlussfolgerung: Die Daten weisen auf eine Zellschädigung infolge der absorbierten Dosis hin ohne erkennbaren Einfluss von heterogenen, intrazellulären Radionuklidverteilungen. Nach intrazellulärer Aufnahme wurde mittels alkalischen und neutralen Komet-Assay keine Zunahme der Komplexität von DNA-Schäden beobachtet. Die Aufnahme von 99mTc und 211At führt zur Dosissteigerung und der Reduktion des klonogenen Zellüberlebens.

Keywords

Auger emitters - radionuclides - clonogenic cell survival - comet assay - 99mTc - 211At - sodium iodide symporter - radiobiology

Schlüsselwörter

Auger-Emitter - Natrium-Iodid-Symporter - 99mTc - 211At
 

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