Studies of Benign and Malignant Thyroid Disease

良性和恶性甲状腺疾病的研究

基本信息

批准号：
10700666
负责人：
Joanna Klubo-Gwiezdzinska
金额：
$ 33.07万
依托单位：
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10700666
关键词：
Adult Askenazy Cells Benign Blood specimen Cancer cell line Diagnosis Diagnostic Epigenetic Process Excision Experimental Designs Fine needle aspiration biopsy Goals Human In Vitro Incidence Malignant - descriptor Malignant Neoplasms Malignant neoplasm of thyroid Methods Modeling Molecular Molecular Target Multiple Endocrine Neoplasia Type 2a Natural History Neoplasm Metastasis Nodule Operative Surgical Procedures Outcome PET/CT scan Patient Participation Patients Prognosis Protocols documentation Radioactive Iodine Radiolabeled Rattus Recurrent disease Role SSTR2 gene Sampling Scanning Specimen Study Subject Techniques Testing Thyroid Diseases Thyroid Gland Thyroid Nodule Tissue Sample Tissues Translating Treatment Efficacy X-Ray Computed Tomography Xenograft procedure analog bench to bedside immunohistochemical markers in vivo molecular marker mouse model novel pancreatic cell line patient screening research study somatostatin analog somatostatin receptor 2 standard care targeted imaging targeted treatment testing uptake treatment response tumor uptake

项目摘要

Purpose: The goal of this study was to analyze the role of somatostatin receptor type 2 (SSTR2) as a molecular target for the imaging and treatment of thyroid cancer through analysis of SSTR2 expression and its epigenetic modulation and testing tumor uptake of different radiolabeled SSTR2 analogues. Experimental design: We analyzed SSTR2 expression by immunostaining of 92 thyroid cancer tissue samples and quantified standard uptake values (SUVmax) of SSTR2 analogue, 68Ga-DOTA-TATE, by PET/CT imaging in 25 patients with metastatic thyroid cancer. We utilized human thyroid cancer cell lines characterized by differential SSTR2 expression (TT, BCPAP, and FTC133) and rat pancreatic cell line (AR42J) with intrinsically high SSTR2 expression for functional in vitro studies. SSTR2-high (AR42J) and SSTR2-low (FTC133) xenograft mouse models were used to test the uptake of radiolabeled SSTR2 analogues and their therapeutic efficacy in vivo. Results: Thyroid cancer had a higher SSTR2 expression than normal thyroid. Hurthle cell thyroid cancer was characterized by the highest 68Ga-DOTA-TATE uptake median SUVmax, 16.5 (7.9-29) than other types of thyroid cancers. In vivo studies demonstrated that radiolabeled DOTA-EB-TATE is characterized by significantly higher tumor uptake than DOTA-TATE (P < 0.001) and DOTA-JR11 (P < 0.001). Treatment with 177Lu-DOTA-EB-TATE extended survival and reduced tumor size in a mouse model characterized by high somatostatin (SST) analogues uptake (SUVmax, 15.16 4.34), but had no effects in a model with low SST analogues uptake (SUVmax, 4.8 0.27). Conclusions: A novel SST analogue, 177Lu-DOTA-EB-TATE, has the potential to be translated from bench to bedside for the targeted therapy of patients characterized by high uptake of SST analogues in metastatic lesions.

目的：这项研究的目的是通过分析SSTR2表达及其表观遗传调节以及测试不同放射性标记的SSTR2类似物的肿瘤吸收，分析生长抑素受体2型（SSTR2）作为对甲状腺癌进行成像和治疗的分子靶标。实验设计：我们通过对25例转移性甲状腺癌的25例患者的PET/CT成像对SSTR2类似物的92个甲状腺癌组织样品进行免疫染色和量化的标准摄取摄取值（SUVMAX）分析了SSTR2的表达。我们利用了以差异SSTR2表达（TT，BCPAP和FTC133）和大鼠胰腺细胞系（AR42J）为特征的人类甲状腺癌细胞系（AR42J），其本质上具有较高的SSTR2表达在体外研究中。 SSTR2-高（AR42J）和SSTR2-LOW（FTC133）异种移植小鼠模型用于测试放射性标记的SSTR2类似物的摄取及其在体内的治疗功效。结果：甲状腺癌的SSTR2表达高于正常甲状腺。与其他类型的甲状腺癌相比，赫瑟细胞甲状腺癌的特征是最高的68Ga-Dota-tate摄取中值Suvmax，16.5（7.9-29）。体内研究表明，放射性标记的dota-eb-tate的特征是肿瘤的摄取明显高于dota-tate（p <0.001）和dota-jr11（p <0.001）。用177lu-dota-eb-tate的延长生存期和肿瘤大小降低的小鼠模型中的治疗，其特征在于高生长抑素（SST）类似物的吸收（Suvmax，15.16 4.34），但在模型中没有效果，但SST类似物的吸收率低（Suvmax，Suvmax，4.8 0.27）。结论：一种新型的SST类似物，177lu-dota-eb-tate，有可能从长凳上翻译成床边，以靶向患者的靶向疗法，这些患者的特征是转移性病变中SST类似物的摄取。