mTcO₄--, 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, Mauxion, Thibault, Richard-Fiardo, Peggy, Guglielmi, Julien, Crescence, Lydie, Mari, Bernard, Pourcher, Thierry, Darcourt, Jacques, Bardiès, Manuel, Vassaux, Georges
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science (PLoS) 2014
• Subjects: Animals; Biological Transport; DNA Breaks, Double-Stranded - radiation effects; Electrons; Female; Gene Expression Regulation - radiation effects; Mice; Radiometry; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sodium Pertechnetate Tc 99m - adverse effects; Sodium Pertechnetate Tc 99m - metabolism; Symporters - genetics; Symporters - metabolism; Thyroid Gland - cytology; Thyroid Gland - metabolism; Thyroid Gland - radiation effects; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed
• 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.