Imaging Biomarkers for Glioma Treatment Response

神经胶质瘤治疗反应的成像生物标志物

基本信息

  • 批准号:
    10453751
  • 负责人:
  • 金额:
    $ 21.68万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-01 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Alteration of metabolism so as to favor a preponderance of glycolysis (GLY) relative to oxidative phosphorylation (OXPHOS) is considered a hallmark of cancer. Known originally as the Warburg effect, and now considered part of the larger concept of metabolic reprogramming, these cellular changes represent a way for cancer tissue to support rapid proliferation by preserving carbon skeletons for biomass production. Understanding the mechanisms that underlie this metabolic shift is an active area of research. In the context of therapeutics, insights from recent studies provide strong support that this reprogramming phenotype is necessary and sufficient to support the cancer process, thus providing a basis for highly novel therapeutic strategies in which either blocking or reversing metabolic reprogramming is the goal. Furthermore, malignant gliomas, highly glycolytic cancers exceedingly resistant to conventional treatments, seem particularly suited to approaches that can subvert this phenotype, and we believe the most crucial obstacle to moving such therapies to clinic has been the inability to reliably measure in vivo response to such metabolic therapies. The scientific premise of this proposal is that hyperpolarized 13C (HP13C) magnetic resonance imaging (MRI) offers great promise in fulfilling this clinical need. Pyruvate (Pyr), located at a crucial juncture in the brain glucose metabolic pathway where it can be either reduced to lactate (Lac) or converted to acetyl CoA + CO2, which is then converted to bicarbonate (Bic), has the potential to be used as a HP13C surrogate marker of the balance between GLY and OXPHOS. Following the bolus injection of HP [1-13C]Pyr, we propose that the observed 13C-Lac/13C-Bic (Lac/Bic) ratios can be used as a quantitative biomarker of a changing balance between these two metabolic processes, thus providing key information on glucose’s metabolic fate complementary to the uptake information provided by more commonly available 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET). Here, we propose to add simultaneous FDG-PET/HP13C/MRI measurements to an upcoming Phase II clinical trial of malignant glioma treated with BPM31510 (Berg LLC), a nano-suspension of Coenzyme Q10 showing high accumulation in cancer cell mitochondria and having marked antitumor activity in multiple in vivo models (both alone and in combination with chemotherapeutic agents) with in vitro evidence strongly suggesting the effect is mediated via increasing OXPHOS (i.e., reversing the Warburg effect). Our overall goal is to assess the potential synergy of combining information on glucose uptake, as provided by FDG-PET, and glucose metabolism, as provided by HP13C, for tumor characterization, assessment of therapeutic response, and prediction of patient outcome. If successful, the results from this pilot study would provide the critical preliminary data to justify larger follow-up studies of the use of these imaging biomarkers with anticancer metabolic therapies.
摘要

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Lawrence D Recht其他文献

Lawrence D Recht的其他文献

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{{ truncateString('Lawrence D Recht', 18)}}的其他基金

Imaging Biomarkers for Glioma Treatment Response
神经胶质瘤治疗反应的成像生物标志物
  • 批准号:
    10025488
  • 财政年份:
    2020
  • 资助金额:
    $ 21.68万
  • 项目类别:
Metabolic Therapy of GBM guided by MRS of hyperpolarized 13C-pyruvate
超极化13C-丙酮酸MRS引导的GBM代谢治疗
  • 批准号:
    9262926
  • 财政年份:
    2014
  • 资助金额:
    $ 21.68万
  • 项目类别:
Protocol Review and Monitoring System
方案审查和监控系统
  • 批准号:
    10411089
  • 财政年份:
    2007
  • 资助金额:
    $ 21.68万
  • 项目类别:
Quantifying Cortical Neuron Production After Transplantation
移植后量化皮质神经元的产生
  • 批准号:
    7388436
  • 财政年份:
    2007
  • 资助金额:
    $ 21.68万
  • 项目类别:
CLINICAL TRIAL: DEXAMETHASONE-SPARING STUDY COMPARING (HERF) TO PLACEBO
临床试验:地塞米松节约研究 (HERF) 与安慰剂的比较
  • 批准号:
    7717882
  • 财政年份:
    2007
  • 资助金额:
    $ 21.68万
  • 项目类别:
CLINICAL TRIAL: HCRF FOR PATIENTS WITH MALIGNANT BRAIN TUMOR WHO REQUIRE HIGH-DO
临床试验:HCRF 适用于需要高剂量治疗的恶性脑肿瘤患者
  • 批准号:
    7717889
  • 财政年份:
    2007
  • 资助金额:
    $ 21.68万
  • 项目类别:
CLINICAL TRIAL: PERITUMORAL BRAIN EDEMA IN PATIENTS WITH PRIMARY MALIGNANT GLIOM
临床试验:原发性恶性胶质瘤患者的瘤周脑水肿
  • 批准号:
    7717893
  • 财政年份:
    2007
  • 资助金额:
    $ 21.68万
  • 项目类别:
HCRF FOR PATIENTS WITH MALIGNANT BRAIN TUMOR WHO REQUIRE HIGH-DOSE DEXAMETHASONE
HCRF 适用于需要大剂量地塞米松的恶性脑肿瘤患者
  • 批准号:
    7605237
  • 财政年份:
    2007
  • 资助金额:
    $ 21.68万
  • 项目类别:
CDOn: A Novel Marker of Neuronal Stem Cells
CDOn:神经元干细胞的新型标记物
  • 批准号:
    7647581
  • 财政年份:
    2007
  • 资助金额:
    $ 21.68万
  • 项目类别:
PERITUMORAL BRAIN EDEMA IN PATIENTS WITH PRIMARY MALIGNANT GLIOMA; (HCRF) TO DEX
原发性恶性胶质瘤患者的瘤周脑水肿;
  • 批准号:
    7605243
  • 财政年份:
    2007
  • 资助金额:
    $ 21.68万
  • 项目类别:

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