Morphometric and Functional Changes of Salivary Gland Dysfunction After Radioactive Iodine Ablation in a Murine Model

Abstract

Background: Ablation of the thyroid tissue using radioactive iodine (RAI) after the surgical removal of welldifferentiated thyroid cancer can induce radiation-related salivary gland (SG) dysfunction. However, in vivo changes of SGs after RAI administration in appropriate animal models are not well described in the literature. This study was undertaken to document morphometric and functional changes during the 12 months after RAI administration in a murine model of RAI-induced SG dysfunction. Methods: Four-week-old female C57BL/6 mice (n = 60) were divided into an RAI-treated group (n = 30) that received RAI orally (0.01 mCi/g body weight) and an unexposed control group (n = 30). Mice in both groups were divided into five subgroups (n = 6 per subgroup) and euthanized at 1, 2, 3, 6, and 12 months post-RAI administration. Salivary flow rates and salivary lag times were measured at 1, 2, 3, 6, and 12 months after RAI administration. Morphological and histological examinations and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed. In addition, changes in salivary 99mTc pertechnetate uptake and excretion were observed by single-photon emission computed tomography. Results: In RAI-treated mice, the SGs were significantly lighter than those of unexposed controls at all study time points. Lag times to salivation in the RAI-treated group were greater than in the unexposed controls, but mean salivary flow rates were lower. Histologic examinations of SGs in the RAI group showed pale cytoplasm, atypical ductal configuration, septal widening, cytoplasmic vacuolization with pleomorphism, lymphocyte infiltration, and increased fibrosis. Furthermore, more apoptotic cells were observed in acini and ducts in the RAI group. In addition, patterns of 99m Tc pertechnetate uptake and excretion in the RAI group were quite different from those observed in controls at 1 and 12 months post-RAI. Conclusion: Various histological alterations were observed in mice exposed to RAI, that is, an increase in apoptotic acini and ductal cells and functional SG deterioration. The murine model of RAI-induced SG dysfunction used in the present study appears to be applicable to preclinical research on RAI-induced sialadenitis in patients with well-differentiated thyroid cancer.

Usefulness of Magnetic Resonance Sialography for the Evaluation of Radioactive Iodine-Induced Sialadenitis

“…10 In a previous study, we found RAI-induced histological SG changes such as acinar degeneration and pleomorphism, atypical ductal configuration, peri-acinoductal inflammation, and fibrosis. 4 In the present study, we found that MR sialography depicted abnormal ductal and parenchymal findings. Ductal configurations observed by MR sialography were consistent with those reported in our previous study.…”

“…3 We previously investigated histological changes in RAI-exposed SGs of mice and found that RAI induces marked parenchymal and ductal pathologic changes. 4 Conventional sialography and salivary scintigraphy (SSG) are generally used to evaluate SG hypofunction but this requires an invasive maneuver, and radiation exposure is inevitable for SSG and conventional sialography.Ha Young Lee and Jae-Yol Lim contributed equally to this work.Electronic supplementary material The online version of this article ( …”

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

“…As salivary glands do not possess the ability to organify iodine, retention time of the thyroid-ablative dose of 131 I is limited. Thus, salivary glands are preserved, at least in part, as is their ability to accumulate 99m Tc-pertechnetate, while thyroidal uptake is completely eliminated, as was shown by whole-body and neck transaxial planar SPECT imaging by Choi et al [35]. …”

Salivary gland function after sialendoscopy for treatment of chronic radioiodine‐induced sialadenitis

“…Radioactive iodine ( 131 I) therapy causes acute and late complications as a result of adverse effects of exposure to radiation on normal tissue. Late effects of radioactive iodine on salivary glands are characterized as damage to salivary ductal cells and extend deeply into the soft tissue, causing both parenchymal and vascular cell damage . The specific cellular mechanisms of radioactive iodine‐induced salivary gland injury remain poorly understood, but one of the pathologic effects is thought to be related to a variety of inflammatory mediators leading to fibrotic processes.…”

“…The ß‐radiation emitted by radioactive iodine ( 131 I) damages salivary glands that normally take up 131 I mediated by sodium‐iodide symporter in salivary gland ductal cells . In our previous animal study, we investigated the histological changes in radioactive iodine‐injured murine salivary glands and found that radioactive iodine induced significant parenchymal pathologies, such as atypical ductal configuration, periacinoductal inflammation, and fibrosis . Radioactive iodine‐induced salivary gland damage consequently leads to obstructive sialadenitis presenting recurrent swelling with or without pain during meals.…”