99mTcO4−-, Auger-Mediated Thyroid Stunning: Dosimetric Requirements and Associated Molecular Events

• Published in: PloS one Vol. 9; no. 3; p. e92729
• Main Authors: Cambien, Béatrice, Franken, Philippe R, Lamit, Audrey, Thibault Mauxion, Richard-Fiardo, Peggy, Guglielmi, Julien, Crescence, Lydie, Bernard, Mari, Pourcher, Thierry, Darcourt, Jacques, Bardiès, Manuel, Vassaux, Georges
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01-03-2014
• Subjects: Adenoviruses; Animal tissues; Animals; Augers; Biological effects; Biology and Life Sciences; Cancer therapies; Cell culture; Cell death; Deoxyribonucleic acid; DNA; DNA damage; Dosimetry; Drug dosages; Electrons; Emitters (electron); Energy; Gene expression; Medicine and Health Sciences; Molecular modelling; mRNA; Nuclear medicine; p53 Protein; Physical Sciences; Radioisotopes; Research and Analysis Methods; Sodium; Thyrocytes; Thyroid; Thyroid gland; France
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0092729

Low-energy Auger and conversion electrons deposit their energy in a very small volume (a few nm3) around the site of emission. From a radiotoxicological point of view the effects of low-energy electrons on normal tissues are largely unknown, understudied, and generally assumed to be negligible. In this context, the discovery that the low-energy electron emitter, 99mTc, can induce stunning on primary thyrocytes in vitro, at low absorbed doses, is intriguing. Extrapolated in vivo, this observation suggests that a radioisotope as commonly used in nuclear medicine as 99mTc may significantly influence thyroid physiology. The aims of this study were to determine whether 99mTc pertechnetate (99mTcO4−) is capable of inducing thyroid stunning in vivo, to evaluate the absorbed dose of 99mTcO4− required to induce this stunning, and to analyze the biological events associated/concomitant with this effect. Our results show that 99mTcO4−–mediated thyroid stunning can be observed in vivo in mouse thyroid. The threshold of the absorbed dose in the thyroid required to obtain a significant stunning effect is in the range of 20 Gy. This effect is associated with a reduced level of functional Na/I symporter (NIS) protein, with no significant cell death. It is reversible within a few days. At the cellular and molecular levels, a decrease in NIS mRNA, the generation of double-strand DNA breaks, and the activation of the p53 pathway are observed. Low-energy electrons emitted by 99mTc can, therefore, induce thyroid stunning in vivo in mice, if it is exposed to an absorbed dose of at least 20 Gy, a level unlikely to be encountered in clinical practice. Nevertheless this report presents an unexpected effect of low-energy electrons on a normal tissue in vivo, and provides a unique experimental setup to understand the fine molecular mechanisms involved in their biological effects.