Measuring Metabolic Activity in Prostate Cancer Bone Metastases Using Hyperpolarized 13C Pyruvate MRI for Improved Targeted Therapy Monitoring
使用超极化 13C 丙酮酸 MRI 测量前列腺癌骨转移的代谢活动,以改进靶向治疗监测
基本信息
- 批准号:10307137
- 负责人:
- 金额:$ 65.63万
- 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:2020-12-01 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAddressAffectAndrogen ReceptorAndrogensBiological MarkersBiopsyBone DiseasesBone PainBromodomainCancer ModelCancer PatientCessation of lifeClinicalClinical DataClinical TrialsDataDetectionDevelopmentDiseaseDisseminated Malignant NeoplasmDown-RegulationDrug TargetingEarly treatmentEnrollmentEvaluable DiseaseEvaluationFOLH1 geneFeasibility StudiesFractureGenerationsGoalsHealthHypercalcemiaImageInterdisciplinary StudyInvestigationLactate DehydrogenaseLettersMagnetic Resonance ImagingMalignant NeoplasmsMalignant neoplasm of lungMalignant neoplasm of prostateMeasurementMeasuresMediatingMedicalMetabolicMetastatic Neoplasm to the BoneMetastatic Prostate CancerMethodsMolecularMonitorMorbidity - disease rateNeoplasm MetastasisNoisePathway interactionsPatient imagingPatientsPharmacotherapyPhasePositron-Emission TomographyPrediction of Response to TherapyPyruvateRenal carcinomaResearchResistanceRunningSerumSerum MarkersSignal TransductionSiteTechniquesTechnologyTestingTherapeutic InterventionTimeTranslatingTreatment EffectivenessUnited States National Institutes of HealthWidespread Diseaseadvanced diseaseadvanced prostate cancerantagonistbasebiomarker-drivenbonebone turnoverburden of illnesscancer genomicscastration resistant prostate cancercytopeniadesigndetectordrug developmentearly phase trialenzalutamidefeasibility trialimaging approachimaging biomarkerimaging modalityimprovedin vivoineffective therapiesinhibitorinvestigator-initiated trialmalignant breast neoplasmmetabolic imagingmolecular imagingnew therapeutic targetnovelnovel strategiesnovel therapeuticspatient populationpre-clinicalresponseserum PSAside effectstable isotopetargeted treatmenttherapy developmenttherapy resistanttool developmenttreatment effecttreatment response
项目摘要
Project Summary/Abstract
Prostate cancer is a major US health concern with over 160,000 new cases and 30,000 deaths per year. More
than 90% of patients with advanced disease have bone metastases with a median survival of a year. Patients
with metastatic bone disease suffer from bone pain, fractures, hypercalcemia, cytopenias, and ultimately death.
The goal of this early phase “feasibility” imaging “biomarker-driven” trial is to investigate novel 3D hyperpolarized
(HP) 13C-pyruvate MRI techniques to quantitatively measure lactate dehydrogenase (LDH) catalyzed pyruvate-
to-lactate (kPL) conversion rates in prostate cancer bone metastases to enable early and rapid metabolic
response monitoring to treatment response and development of therapeutic resistance, as well assess on-target
treatment effects for new targeted drug development, thus addressing current unmet clinical needs. This clinical
trial is required because current imaging modalities for bone metastases are inadequate for quantifying response
to therapeutic interventions. This can result in significant delays in determining treatment effectiveness, and
subjecting patients to prolonged periods of side-effects of ineffective therapies, too often causing excess
morbidity without benefit.
Hyperpolarized (HP) 13C-pyruvate MRI is a safe, non-radioactive, quantitative MR stable-isotope imaging
approach that can provide early, real-time metabolic response monitoring of prostate cancer bone metastases.
Added to conventional mpMRI exams, the rapid 2 minute HP MRI measurement of pyruvate-to-lactate
conversion rate, kPL, a potentially valuable “biomarker”, reflects changes in metabolic reprogramming and early
response to targeted therapies (e.g. AR, MYC inhibitors). While PSMA-PET improves detection of metastatic
disease, PSMA expression is not directly affected by targeted therapies including androgen pathway inhibitors
and novel MYC-targeted therapies in clinical trial evaluation, and therefore is not able to reliably capture bone
metastasis response at early time points. HP 13C-pyruvate MR studies have demonstrated that MYC-mediated
increased HP 13C pyruvate-to-lactate metabolic conversion rate, kPL, is associated with key oncogenomic
alterations that occur with the progression to advanced prostate cancer and decreased in response to treatment.
Initial studies also demonstrated that higher kPL is associated with intrinsic resistance to androgen pathway
inhibitors (e.g. enzalutamide). Our multidisciplinary research team translated these findings into patient feasibility
studies and performed first-ever HP 13C-pyruvate metabolic MR imaging of patients with prostate cancer bone
metastases demonstrating feasibility and supporting the scientific rigor of this approach. This new biomarker-
driven trial is designed to apply new HP 13C-pyruvate MRI technology for monitoring androgen-receptor and MYC
targeted drug therapies with the goal of investigating kPL as a quantitative in vivo marker to measure metabolic
changes with treatment in patients with bone-tropic advanced prostate cancer.
项目总结/摘要
前列腺癌是美国主要的健康问题,每年有超过160,000例新发病例和30,000例死亡。更
超过90%的晚期疾病患者有骨转移,中位生存期为一年。患者
患有转移性骨疾病的患者遭受骨痛、骨折、高钙血症、血细胞减少,并最终死亡。
这项早期“可行性”成像“生物标记驱动”试验的目标是研究新型3D超极化
(HP)13 C-丙酮酸MRI技术定量测量乳酸脱氢酶(LDH)催化的丙酮酸-
前列腺癌骨转移中的乳酸(kPL)转化率,以实现早期和快速的代谢
监测治疗反应和治疗耐药性的发展,以及评估达标情况
新靶向药物开发的治疗效果,从而解决当前未满足的临床需求。本临床
需要进行试验,因为目前骨转移的成像方式不足以量化缓解
到治疗干预。这可能导致在确定治疗有效性方面的显著延迟,并且
使患者长期遭受无效治疗的副作用,
没有好处的疾病。
超极化(HP)13 C-丙酮酸盐MRI是一种安全、非放射性、定量MR稳定同位素成像
这种方法可以提供前列腺癌骨转移的早期、实时代谢反应监测。
在常规mpMRI检查的基础上,使用快速2分钟HP MRI测量乳酸盐/乳酸盐比值,
转化率,kPL,一个潜在的有价值的“生物标志物”,反映了代谢重编程和早期代谢的变化。
对靶向治疗(例如AR、MYC抑制剂)的反应。虽然PSMA-PET改善了转移性乳腺癌的检测,
PSMA表达不直接受靶向治疗(包括雄激素途径抑制剂)的影响
和新的MYC靶向疗法,因此不能可靠地捕获骨
在早期时间点的转移反应。HP 13 C-丙酮酸盐MR研究表明,MYC介导的
HP 13 C代谢转化率(kPL)增加与关键癌基因组相关,
随着进展到晚期前列腺癌而发生的改变,并在治疗后减少。
初步研究还表明,较高的kPL与雄激素途径的内在抵抗有关
抑制剂(例如恩杂鲁胺)。我们的多学科研究团队将这些发现转化为患者的可行性
研究并首次对前列腺癌骨患者进行HP 13 C-丙酮酸代谢MR成像
转移证明了可行性并支持这种方法的科学严谨性。新的生物标记物-
一项旨在应用新的HP 13 C-丙酮酸MRI技术监测雄激素受体和MYC的驱动试验
靶向药物治疗,目的是研究kPL作为定量体内标记物,
嗜骨性晚期前列腺癌患者治疗后的变化。
项目成果
期刊论文数量(0)
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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Rahul Aggarwal其他文献
Rahul Aggarwal的其他文献
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{{ truncateString('Rahul Aggarwal', 18)}}的其他基金
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免疫治疗与分子靶向放射治疗相结合
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Precision targeting of T cell cytotoxicity with PET
使用 PET 精确靶向 T 细胞的细胞毒性
- 批准号:
10352453 - 财政年份:2021
- 资助金额:
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Precision targeting of T cell cytotoxicity with PET
使用 PET 精确靶向 T 细胞的细胞毒性
- 批准号:
10561714 - 财政年份:2021
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Precision targeting of T cell cytotoxicity with PET
使用 PET 精确靶向 T 细胞的细胞毒性
- 批准号:
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Measuring Metabolic Activity in Prostate Cancer Bone Metastases Using Hyperpolarized 13C Pyruvate MRI for Improved Targeted Therapy Monitoring
使用超极化 13C 丙酮酸 MRI 测量前列腺癌骨转移的代谢活动,以改进靶向治疗监测
- 批准号:
10523532 - 财政年份:2020
- 资助金额:
$ 65.63万 - 项目类别:
Targeting Neuroendocrine Prostate Cancer Using Multi-Probe Hyperpolarized 13C MRI for Improved Treatment and Therapeutic Monitoring
使用多探头超极化 13C MRI 靶向神经内分泌前列腺癌以改善治疗和治疗监测
- 批准号:
9925733 - 财政年份:2017
- 资助金额:
$ 65.63万 - 项目类别:
Targeting Neuroendocrine Prostate Cancer Using Multi-Probe Hyperpolarized 13C MRI for Improved Treatment and Therapeutic Monitoring
使用多探头超极化 13C MRI 靶向神经内分泌前列腺癌以改善治疗和治疗监测
- 批准号:
10163810 - 财政年份:2017
- 资助金额:
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