124I-NaI PET: Building block for precision medicine in metastatic thyroid cancer

124I-NaI PET：转移性甲状腺癌精准医疗的基石

基本信息

批准号：
9976468
负责人：
JOHN L HUMM
金额：
$ 72.34万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-05 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9976468
关键词：
Ablation Alternative Therapies Avidity BRAF gene Biological Cancer Patient Clinic Clinical Clinical Trials Data Development Diagnostic Discipline of Nuclear Medicine Disease Disease Management Distant Metastasis Dose Dysmyelopoietic Syndromes Dysplasia ERBB3 gene Endocrinologist Evaluation Gamma Rays Gene Expression Genes Genetic Transcription Genomics Genotype Goals Heterogeneity Hospitals I131 isotope Image Individual Institution Investigation Iodides Iodine Lacrimal Duct Obstruction Lesion Life Lung MAP Kinase Gene MAP3K1 gene MEKs Malignant Neoplasms Malignant neoplasm of thyroid Marrow Measurement Measures Medical Oncologist Medicine Metabolism Methodology Methods Molecular Monoclonal Antibodies Morbidity - disease rate Motion Neoplasm Metastasis Normal tissue morphology Output Pathway interactions Patient Care Patient Selection Patients Persons Pharmaceutical Preparations Physicians Physics Positron-Emission Tomography Protein-Serine-Threonine Kinases Protocols documentation Radiation Radiation Oncologist Radiation Tolerance Radioactive Iodine Recommendation Refractory Refractory Disease Research Respiration Risk Role Salivary Glands Savings Stable Disease Structure Surgeon Testing Therapeutic Time Tissues Toxic effect Tracer Treatment Efficacy Treatment Protocols Validation X-Ray Computed Tomography base clinical practice dosimetry experience imaging modality improved in vivo individual patient inhibitor/antagonist leukemia man novel novel therapeutics partial response patient subsets pilot trial precision medicine predictive test programs quantitative imaging radioiodine therapy respiratory responders and non-responders response side effect standard of care therapy design tool treatment optimization treatment strategy tumor unnecessary treatment uptake

项目摘要

Project Summary/Abstract Precision medicine promotes matching an individualized diagnostic and treatment strategy to the functional and molecular composition of each person’s particular cancer(s). The goal of the current proposal is to apply precision medicine to the unmet need of optimal patient selection for radioiodine treatment (RAI) of metastatic thyroid cancer. Our proposal is based on measuring individual lesion dosimetry using 124I-NaI PET. The clinical problem is highly significant and the potential impact is high; distant metastases are identified in 10-15% of patients with differentiated thyroid cancer during the course of their disease, and for more than 50 years, RAI has been the standard of care for patients with structurally evident RAI-avid distant metastases. Multiple administered doses greater than 150 mCi are often required to obtain durable responses even in small volume disease. Moreover, toxicity of high-dose RAI regimens is significant, causing salivary gland damage in many patients and occasionally marrow dyscrasias, and even leukemia. In present clinical practice, dosing and patient selection are largely empirical. Thus, many patients receive repeated ineffective doses of RAI therapy, resulting in considerable morbidity without therapeutic gain. We propose a novel paradigm to select patients who stand to benefit from RAI based on an 124I PET metric that could identify patients with sufficient RAI uptake in their tumors to respond. More importantly, it would identify patients unlikely to achieve therapeutic efficacy from RAI who would be spared unnecessary treatment and the associated risks of serious side effects. We recently showed that lesional dosimetry estimates with 124I correctly identified a subset of previously non- radioiodine-avid patients who had radioiodine avidity restored by the MEK inhibitor selumetinib sufficient for structural responses to radioiodine therapy, as determined by RECIST criteria. Our proposal will dovetail with MEK and BRAF inhibitor trials and offer treatment decision criteria with which to evaluate the benefits of RAI in the context of these new medicines. If successful, this proposal will result in the development of a minimalist practical protocol that will impact all thyroid cancer patients with distant metastases being considered for additional RAI therapy, as this 124I methodology can be employed in all hospitals with a PET scanner. The objectives of our proposed approach include: 1) phantom validation of 124I quantification, which accounts for cascade coincidence gammas, respiration (for lung lesions), and partial volume corrections; 2) lesion dosimetry quantification by serial 124I PET, using the data to develop a simplified imaging paradigm to determine the achievability of a therapeutic radioiodine dose, as well as to correlate the lesional dose with structural response; 3) investigation of genomic correlates of lesion uptake and response; and 4) exploration of concurrent imaging and therapy approaches in which 124I is administered in the presence of therapeutic doses of 131I—first in phantoms and then in man to document “real-time” tumor dose.

项目摘要/摘要精密医学可促进匹配与功能的个性化诊断和信任策略相匹配和每个人的特定癌症的分子组成。精密医学，可用于放射性碘治疗（RAI）转移性的最佳tim毛甲状腺癌基于使用124-NAI PET测量单个病变问题非常重要，潜在的影响很高；患有分化的甲状腺癌的患者在疾病过程中，超过50年，RAI 一直是具有结构明显Rai avid远处转移的护理人员的标准。通常需要大于150 mci的剂量以获得持久的反应此外，疾病。患者有时会在目前的临床实践和剂量中，甚至是白血病。患者的选择是更大的经验。由于治疗性增长，我们提出了一个新的范式，以选择患者。谁将根据124i PET度量从RAI中受益，该指标可以识别有权RAI的患者肿瘤的吸收更重要的是，它可以识别出患者 RAI的功效将是不必要的治疗方法，并带来严重副作用的相关风险。我们最近表明，具有124i的病变剂量法估计值正确鉴定 MEK抑制剂selumetinib恢复了放射碘亲和力的放射性二胺avid患者根据RECIST标准确定的对放射性碘治疗的结构反应。通过MEK和BRAF抑制剂试验，并提供治疗决策标准，以评估在新药物的背景下，RAI如果成功的话，该建议将导致极简主义实用方案甲状腺癌患者患有DITH DITHID癌患者考虑进行其他RAI治疗，因为该124i方法可以在宠物的医院中使用扫描仪。级联重合伽玛，呼吸（用于肺部病变）和部分体积校正；通过数据使用数据来开发简化的成像范例，通过串行124i PET进行病变剂量测定。确定sherapeutic放射性碘剂量的成就结构反应； 3）研究病变的基因组相关性同时进行的成像和治疗方法，其中124i在治疗剂量的存在下进行幻象和这些“实时”肿瘤剂量的131i优先。