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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.

项目总结/文摘