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Novel Bisphosphonate PET Probes for Myeloma Bone Disease

用于骨髓瘤骨病的新型双膦酸盐 PET 探针

基本信息

批准号：
10405086
负责人：
Kai Chen
金额：
$ 22.68万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-13 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10405086
关键词：
Anatomy Animals Area B cell differentiation Bone Diseases Bone Marrow Bone Marrow Involvement Bone Pain Bone Resorption Bone neoplasms Bone remodeling COVID-19 pandemic Cells Characteristics Chemistry Chest Clinic Clinical Clonal Expansion Complication Cyclotrons Data Detection Development Diagnosis Diagnostic Disadvantaged Disease Disease Management Disease Progression Dose Early Diagnosis Emergency Situation Emission-Computed Tomography Esters Femur Flare Fluorine Foundations Future Generations Goals Gold Half-Life Healthcare Systems Hematologic Neoplasms Human Image Imaging technology In Situ Innate Bone Remodeling Investigation Label Laboratories Lesion Long-Term Care Lytic Lytic Metastatic Lesion Magnetic Resonance Imaging Malignant Neoplasms Measures Medical Imaging Modeling Molecular Molecular Weight Monitor Morbidity - disease rate Multiple Myeloma Mus Neurologic Deficit Newly Diagnosed Oncology Osteoblasts Osteogenesis Osteolysis Pain Pathological fracture Patients Pelvis Pharmaceutical Preparations Pharmacology Phase Physicians Physiological Plasma Cells Positron-Emission Tomography Preparation Procedures Process Production Quality of life Radiochemistry Radioisotopes Reaction Recording of previous events Rodent Model Safety Sampling Site Skeletal Survey Solid Source Specificity Staging Symptoms Technology Time Translating Vertebral column X-Ray Computed Tomography X-Ray Medical Imaging base bisphosphonate bone bone loss bone turnover clinical decision-making cost cranium design disability disease diagnostic fluorodeoxyglucose imaging agent imaging facilities imaging modality imaging probe improved in vivo individual patient innovation low dose computed tomography medical schools molecular imaging mortality novel personalized medicine radiochemical radiological imaging safety study small molecule success treatment optimization treatment response treatment strategy

项目摘要

PROJECT SUMMARY/ABSTRACT Multiple myeloma (MM), a malignancy of mature plasma cells, is the second most common hematologic malignancy. Myeloma bone disease (MBD) is a devastating complication of MM. More than 80% of MM patients suffer from destructive bone lesions, leading to severe pain, pathologic fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also dramatically increases the cost of management. While recent advances in MM therapy have significantly increased the median survival of newly diagnosed patients, osteolytic lesions and their sequelae continue to be a major source of patient morbidity and mortality, and bone pain is the most frequent presenting symptom of MM patients. Rapid improvements in imaging technology now allow physicians to identify ever smaller osteolytic lesions and bone marrow abnormalities, however the clinical value of anatomic findings is not always clear. Therefore, earlier detection and more specific non-invasive assessment of treatment response is urgently needed, to assist in the clinical decision-making process and enable treatment optimization for the individual patient (“personalized medicine”). In this exploratory R21 application we propose novel 18F-BP-PET imaging probes to provide MBD patients a more sensitive measure of osteolytic lesions prompting them to take advantage of new treatment strategies known to improve survival in this group. It is our goal to show that these innovative BP-PET probes can overcome some of the disadvantages of current imaging strategies for MM and provide earlier diagnosis of MBD. Our long- term objective is to translate this new platform into the clinic as a more effective probe for imaging, detecting and staging MBD. Our innovative chemistry design offers rapid preparation (within one 18F half-life) of the proposed PET probes. Cold chemistry will be performed at the USC UPC laboratories by Dr. Charles McKenna and his team, and then elaborated for radiochemistry requirements with Dr. Kai Chen’s group at the USC HSC laboratories. All radiochemistry, including in situ cyclotron generation of the radioisotope 18F, as well as the in vivo animal studies and PET imaging will be performed under Dr. Kai Chen’s direction at the USC Molecular Imaging Center. The optimized radiosynthesis procedure will be validated in an automated synthesis module for future clinical production. To document the imaging efficacy of novel 18F-BP-PET probes, we will use 18F-FDG and 18F-NaF as control imaging agents in a rodent model of MM which reliably results in related bone lesions and compare them with our best novel probe to determine relative sensitivity, ability to detect early bone lesions, specificity and aptness to monitor treatment response. The successful completion of these proof-of-concept studies will serve as a solid foundation for next phase translational development.

项目总结/文摘