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:
  • 金额:
    $ 22.68万
  • 依托单位:
  • 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

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

项目成果

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Kai Chen其他文献

Kai Chen的其他文献

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{{ truncateString('Kai Chen', 18)}}的其他基金

Extreme Heat and Acute Myocardial Infarction: Effect Modifications by Sex, Medical History, and Air Pollution
酷热和急性心肌梗塞:性别、病史和空气污染的影响
  • 批准号:
    10709134
  • 财政年份:
    2023
  • 资助金额:
    $ 22.68万
  • 项目类别:
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
  • 批准号:
    10616547
  • 财政年份:
    2021
  • 资助金额:
    $ 22.68万
  • 项目类别:
IMAT‐ITCR Collaboration: Preclinical Evaluation of Novel Bisphosphonate PET Probes for Myeloma Bone Disease
IMAT-ITCR 合作:新型双膦酸盐 PET 探针治疗骨髓瘤骨病的临床前评估
  • 批准号:
    10461625
  • 财政年份:
    2021
  • 资助金额:
    $ 22.68万
  • 项目类别:

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