Defining the Hypoxic Immunosuppressive Microenvironment as a Biomarker of Therapy Efficacy in Glioblastoma Using Iron Oxide Enhanced FMISO PET/MRI
使用氧化铁增强 FMISO PET/MRI 将缺氧免疫抑制微环境定义为胶质母细胞瘤治疗效果的生物标志物
基本信息
- 批准号:10171809
- 负责人:
- 金额:$ 24.57万
- 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:2020-06-01 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAdjuvantAnxietyAreaBiologicalBiological MarkersBiometryBiopsyCaliforniaCell SurvivalClinicClinicalClinical TrialsDevelopmentDevelopment PlansDiagnosticDiagnostic radiologic examinationDoctor of PhilosophyDrug Delivery SystemsFacultyFlow CytometryFundingFutureGadoliniumGlioblastomaGoalsGrantHealth SciencesHourHumanHypoxiaImageImage Guided BiopsyImmunohistochemistryImmunologistImmunosuppressionImmunotherapeutic agentImmunotherapyInfiltrationInflammatoryInterdisciplinary StudyInvestigational TherapiesIronKnowledgeLaboratoriesLeadLifeMagnetic Resonance ImagingMeasuresMediatingMedicalMentorsMicrogliaModelingMonitorNeurobiologyNeurologicOncologyOperative Surgical ProceduresOregonOutcomePatientsPhagocytesPhenotypePhysiciansPlayPositron-Emission TomographyPre-Clinical ModelPrimary Brain NeoplasmsPrognosisRadiology SpecialtyRattusRecurrent diseaseReportingResearchResearch EthicsResearch PersonnelResourcesReview LiteratureRoleSan FranciscoScientistSubgroupTechniquesTestingTherapeuticTimeTissuesTrainingTranslatingTranslational ResearchTreatment EfficacyTumor-associated macrophagesUncertaintyUniversitiesValidationWorkWritingantitumor effectbasebrain surgerycareercareer developmentchemoradiationclinical trial implementationclinically relevantclinically translatablecollaborative environmenteffective therapyefficacious treatmentexperienceferumoxytolimaging biomarkerimmune activationimprovedinnovationiron oxidemolecular imagingnanoparticleneuroinflammationpatient derived xenograft modelpembrolizumabpre-clinicalprematureprofessorprognosticprognostic of survivalprogramsprospectiveresearch and developmentresponseresponse biomarkerskillsstandard of caretemozolomidetherapy resistanttreatment responsetumortumor hypoxiatumor immunologytumor-immune system interactions
项目摘要
ABSTRACT
This K08 proposal describes a 5-year career development plan with the goal of supporting Dr. Ramon Francisco
Barajas’ advancement to the role of independent early stage physician-scientist. Dr. Barajas has completed
clinical training in Diagnostic Radiology and Neurological Radiology at the University of California, San Francisco
and is currently Assistant Professor in the Departments of Radiology and Advanced Imaging Research Center
at Oregon Health & Science University (OHSU). Edward Neuwelt MD, an expert in drug delivery and molecular
imaging with a strong record of training physician-scientists, will serve as principle mentor. Lisa Coussens PhD,
renowned tumor immunologist; Kenneth Krohn PhD, positron emission tomography (PET) imaging expert;
William Rooney PhD, neurobiology magnetic resonance imaging (MRI) expert; and Rochelle Fu PhD, expert
clinical trial biostatistician, will serve as co-mentors. This project proposes Dr. Barajas’ undertake further training
in preclinical glioblastoma models, human glioblastoma PET/MRI clinical trial implementation and management,
tumor immunology, research ethics, grant writing and biostatistics by means of prospective research and formal
course work. OHSU has a rich and collaborative environment, with a strong commitment to promoting career
development for early stage faculty. Dr. Barajas will be provided with at least 80% protected research time
making OHSU an ideal setting to carry out this program for transitioning to an independently funded research
career. The long-term scientific objective is to define innovative biomarkers of glioblastoma therapeutic
resistance. Neuroinflammation (pseudoprogression) is a hallmark of effective therapy and prognostic of overall
survival. However, pseudoprogression and recurrent disease appear identical by standard of care gadolinium
enhanced MRI (Gd-MRI). Changes within the hypoxic immune microenvironment may serve as biomarkers of
effective therapy and unique feature of pseudoprogression development. A critically unmet clinical need for
immunotherapeutic response assessment is the ability to monitor the hypoxic immune microenvironment. We
address this significant gap in knowledge by pursuing two specific aims: 1) Define glioblastoma immunotherapy-
mediated innate immune activation and tumoricidal efficacy by 11.75T Ferumoxytol (Fe)-MRI, and 2) Determine
if Ferumoxytol-enhancement and hypoxic volume are imaging profiles of glioblastoma immunotherapy-mediated
pseudoprogression or true progression in a clinical trial. Preclinical glioblastoma models (aim 1) and human
clinical trials (aim 2) will be undertaken. The overall hypothesis is that Gd- and Fe-enhanced FMISO PET/MRI
can assess the biological features responsible for immunotherapy efficacy. This translational research and
career development proposal will support a mentored early stage investigator in this area of multidisciplinary
research to directly address the major challenges of developing life prolonging therapeutic approaches for
primary brain tumors; the validation of imaging biomarkers capable of specifically monitoring therapeutic efficacy.
摘要
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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Ramon Francisco Barajas其他文献
Ramon Francisco Barajas的其他文献
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{{ truncateString('Ramon Francisco Barajas', 18)}}的其他基金
Defining the Hypoxic Immunosuppressive Microenvironment as a Biomarker of Therapy Efficacy in Glioblastoma Using Iron Oxide Enhanced FMISO PET/MRI
使用氧化铁增强 FMISO PET/MRI 将缺氧免疫抑制微环境定义为胶质母细胞瘤治疗效果的生物标志物
- 批准号:
10409721 - 财政年份:2020
- 资助金额:
$ 24.57万 - 项目类别:
Defining the Hypoxic Immunosuppressive Microenvironment as a Biomarker of Therapy Efficacy in Glioblastoma Using Iron Oxide Enhanced FMISO PET/MRI
使用氧化铁增强 FMISO PET/MRI 将缺氧免疫抑制微环境定义为胶质母细胞瘤治疗效果的生物标志物
- 批准号:
9892846 - 财政年份:2020
- 资助金额:
$ 24.57万 - 项目类别:
Defining the Hypoxic Immunosuppressive Microenvironment as a Biomarker of Therapy Efficacy in Glioblastoma Using Iron Oxide Enhanced FMISO PET/MRI
使用氧化铁增强 FMISO PET/MRI 将缺氧免疫抑制微环境定义为胶质母细胞瘤治疗效果的生物标志物
- 批准号:
10650734 - 财政年份:2020
- 资助金额:
$ 24.57万 - 项目类别:
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