Risk Factors of Salivary Gland Dysfunction in Radioiodine Treated Thyroid Cancer Patients and Automation of SPECT/CT Imaging Analysis of Mouse Thyroid

摘要

Radioactive iodine-131 is an effective treatment of follicular-cell derived thyroid cancer due to maintained Na+/I- symporter (NIS) expression in well-differentiated thyroid cancer. In normal thyroid tissue, NIS facilitates uptake of iodide into the thyroid for thyroid hormone production and this is exploited in thyroid cancer treatment. NIS is also expressed in the salivary glands leading to transient or even chronic salivary gland damage and dysfunction in some 131I-treated thyroid cancer patients. Because thyroid cancer's five year survival rate is over 95%, quality of life is particularly important in these patients and effective means of predicting who will develop 131I-induced salivary gland damage and how to prevent it have not been found. Pre-clinical microSPECT/CT imaging is used to quantitate radioiodine accumulation and is instrumental for studies identifying strategies to modulate NIS expression both in the salivary glands and in thyroid tumor models of poorly or undifferentiated thyroid cancer that have decreased or no NIS expression. Optimization of image acquisition and analysis would improve these studies.;Sialadenitis and xerostomia are major adverse effects of 131I therapy in thyroid cancer patients. The risk factors for these adverse effects, other than administered activity of 131I, had not previously been investigated. In an initial study of symptom questionnaires from 216 thyroid cancer patients and a validation study search of 1507 thyroid cancer patients' medical records for ICD9/10 codes for sialadenitis, xerostomia, and autoimmune diseases associated with Sjogren's syndrome (AID-SS) were performed to identify clinical and demographic risk factors of 131I-induced sialadenitis and xerostomia. We confirmed that 131I treatment associated with higher incidence of xerostomia and sialadenitis. Additionally, we found patients with xerostomia had significantly higher mean cumulative and first administered 131I activity and that increased age associated with higher incidence of xerostomia. Female gender and a history of sialadenitis associated with higher incidence of sialadenitis after 131I administration. AID-SS associated with higher incidence of both xerostomia and sialadenitis among 131I-treated patients. We conclude that risk factors for 131I-induced salivary gland damage include administered 131I activity, age, gender, history of sialadenitis before 131I treatment, and AID-SS diagnosis.;The ability of thyroid follicular cells to take up and retain iodine enables the use of radioactive iodine (RAI) for imaging and targeted killing of RAI-avid thyroid cancer following thyroidectomy. To preclinically identify novel strategies to improve 131I therapeutic efficacy for patients with non-RAI-avid disease or with poor response to 131I therapy, it is desired to optimize the workflow of imaging acquisition and enhance the capability of imaging analysis for preclinical mouse models of thyroid tumor. We implemented the use of a customized mouse cradle to facilitate consistent tissue configuration across images and developed an in-house CTViewer software to streamline imaging analysis. Consistent mouse tissue configuration allowed for rigid body registration of microSPECT/CT images acquired 1 hour (t1) and 24 hours (t24) after 123I injection. Because the thyroid retains iodine while the salivary glands do not, this alignment allowed automatically threshold-based thyroid volumes of interest (VOI) segmented in the t24 image to be superimposed on the corresponding aligned t1 image to distinguish the thyroid from adjacent salivary glands in t1 images. Furthermore, the extent of heterogeneity in 123I accumulation within thyroid VOIs can be visualized by 3D display of voxel-based 123I gamma photon intensity. These advances will greatly facilitate preclinical mouse studies to uncover novel strategies to improve 131I therapeutic efficacy for patients with advanced thyroid cancer.;Administration of 131I is a common and effective means to treat follicular-cell derived thyroid cancer; however it can be further improved to minimize side effects and increase efficacy in patients with advanced disease. Our retrospective studies of 131I-induced salivary gland damage indicate administered 131I activity, age, gender, history of sialadenitis before 131I treatment, and AID-SS diagnosis are risk factors of 131I-induced salivary gland damage. Additionally, we report methods that have eliminated user subjectivity in analysis of 123I microSPECT/CT imaging where images were taken at t1 and t24 and a method to minimize user subjectivity in studies where only a t1 image is available. This optimization of pre-clinical microSPECT/CT imaging acquisition and analysis will assist in studies to identify novel strategies to increase radioisotope accumulation in thyroid cancer.