PURPOSE: We sought to further localize radioiodine activity in the mouth on post-thyroid cancer therapy imaging using single-photon emission computed tomography/computed tomography (SPECT/CT). MATERIALS AND METHODS: We retrospectively reviewed all patients (58) who underwent thyroid cancer therapy with iodine-131 (I) at our institution from August 2009 to March 2011 whose post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of diagnostic I scans including SPECT/CT was also reviewed. Separately, we performed in-vitro I (sodium iodide) binding assays with amalgam and Argenco HP 77 (77% dental gold alloy) as proof of principle for these interactions. RESULTS: Of the 58 post-therapy patients, 45 (78%) had undergone metallic dental restorations, and of them 41 (91%) demonstrated oral I activity localizing preferentially to those restorations. It was observed that radioiodine also localized to other dental restorations and to orthodontic hardware. Gum-line activity in edentulous patients suggests radioiodine interaction with denture adhesive.In vitro, dental amalgam and Argenco HP 77 bound I in a time-dependent manner over 1-16 days of exposure. Despite subsequent washings with normal saline, significant I activity (maximally 12% for amalgam and 68% for Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated solution of potassium iodide partially displaced I from amalgam, with near-total displacement of I from Argenco HP 77. CONCLUSION: SPECT/CT shows that radioiodine in the oral cavity localizes to metallic dental restorations. Furthermore, in-vitro studies demonstrate partially reversible binding of I to common dental metals. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.