Preclinical microphysiological tumor models for nuclear medicine
核医学临床前微生理肿瘤模型
基本信息
- 批准号:10587674
- 负责人:
- 金额:$ 52.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-01-01 至 2027-12-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAddressAnimal Cancer ModelAnimal ModelBiocompatible MaterialsBiologicalBiological AssayBiological MarkersBiological ProcessBiological TestingBlood VesselsCancer DiagnosticsCancer ModelCancer PatientCapillary PermeabilityCell Culture TechniquesCell ProliferationCellsCharacteristicsClinicalClinical ResearchClinical TrialsComplementDataDedicationsDevelopmentDevice DesignsDiagnosticDiagnostic ImagingDiscipline of Nuclear MedicineEndothelial CellsEngineeringEnvironmentExtracellular MatrixFoundationsFutureGoalsHead and Neck Squamous Cell CarcinomaHumanHypoxiaImageImaging DeviceIn VitroLaboratoriesMeasuresMetabolicMetabolismMicrofabricationMicrofluidic MicrochipsMicrofluidicsMicroscopyModelingMolecularMusOncologyOpticsOrganoidsPatient imagingPatientsPerfusionPharmacologic SubstancePhysiologicalPhysiologyPilot ProjectsPositronPositron-Emission TomographyProceduresProcessPropertyRadiation therapyRadioisotopesRadionuclide ImagingRadiopharmaceuticalsReproducibilityResearchResearch PersonnelResolutionRunningSamplingScienceSolid NeoplasmSystemTherapeuticTissue EngineeringTissuesTracerTranslatingTreatment ProtocolsTumor TissueValidationVascularizationVisualizationWith lateralityWorkX-Ray Computed TomographyXenograft ModelXenograft procedureanticancer researchbiomedical imagingcancer imagingchemotherapyclinical imagingclinical translationclinical trial on a chipclinically relevantcohortcostdrug discoveryexperiencefluorodeoxyglucosefluorodeoxyglucose positron emission tomographyhead and neck cancer patientimage translationimaging approachimaging modalityin vivoindividual patientinstrumentinterestmetermicroPETneovasculaturenovel therapeuticspatient responseperfusion imagingpersonalized medicinepre-clinicalpre-clinical researchpreclinical studypreclinical trialpredictive testprospectivequantitative imagingradiotracerresponseroutine imagingstandard of carestem cellstraffickingtranslational studytreatment responsetumortumor microenvironmenttumor xenograftuptakevascular tissue engineering
项目摘要
Abstract
This project addresses the current lack of quantifiable and clinically relevant imaging endpoints for use in
patient-derived organoid models. Microphysiological tumor models (μPTMs) are tissue-engineered 3D tumors
that can be grown inside microfluidic devices to form multicellular tissue-like constructs that retain the
biological and functional characteristics of the tissue of origin. These μPTMs provide a powerful model of
individual patients’ tumor and are used in drug discovery, cancer research, and personalized medicine.
However, a critical hurdle remains that, unlike xenotransplanted tumors, μPTMs are incompatible with positron
emission tomography (PET) and other diagnostic imaging tools used in oncology. There is a dearth of
quantitative imaging methods that can be applied seamlessly across physical scales, ranging from in vitro cell
cultures to animal models and cancer patients. Drawing from extensive preliminary work, we will bridge this
gap by harnessing the ability of radioluminescence microscopy (RLM) to image clinical radionuclides in
organoids with ultra-high spatial resolution. Upon completion, this project will enable routine imaging of in vitro
tumor models using the growing array of diagnostic and therapeutic radiopharmaceuticals, many of which are
used as clinical standard of care. This goal will be achieved by pursuing three specific aims. First, we will
demonstrate that quantitative image-based metrics can be acquired using PET tracers in patient-derived
organoids. Validation will be conducted for three PET tracers against mouse xenograft models derived from the
same set of cancer patients. Second, we will refine the μPTMs by incorporating functional (perfusable) human
microvascular networks within the 3D matrix and, using imaging and other assays, determine the effect of the
vasculature on image-based endpoints. Third, as a pilot translational study, we will develop patient-specific
μPTMs (n=10) and compare fluorodeoxyglucose (FDG) metabolic activity in these organoids against
biomarkers derived from clinical FDG-PET. In sum, this project will enhance the ability of researchers to run
clinical trials “on a chip”, using the patient’s own tumor and clinically approved radiopharmaceuticals.
Ultimately, these advances could be translated to predict the efficacy of new drugs, test biological hypotheses,
and individualize patient therapy.
摘要
该项目解决了目前缺乏可量化的和临床相关的成像终点,用于
患者来源的类器官模型。微生理学肿瘤模型(μ PTM)是组织工程3D肿瘤
其可以在微流体装置内生长以形成多细胞组织样构建体,
来源组织的生物学和功能特性。这些μ PTM提供了一个强大的模型,
用于治疗个体患者的肿瘤,并用于药物发现,癌症研究和个性化医疗。
然而,一个关键的障碍仍然是,与异种移植肿瘤不同,μ PTM与正电子不相容。
发射断层扫描(PET)和其他用于肿瘤学的诊断成像工具。有一个缺乏
定量成像方法可以无缝地应用于整个物理尺度,从体外细胞
培养到动物模型和癌症患者。通过广泛的前期工作,
利用放射性发光显微镜(RLM)对临床放射性核素成像的能力,
具有超高空间分辨率的类器官完成后,该项目将使常规成像的体外
肿瘤模型使用越来越多的诊断和治疗放射性药物,其中许多是
作为临床护理标准。这一目标将通过实现三个具体目标来实现。一是
证明可以使用PET示踪剂在患者来源的
类器官将对三种PET示踪剂进行针对源自以下的小鼠异种移植模型的验证:
同一组癌症患者。第二,我们将通过将功能性(可灌注的)人
在3D矩阵内的微血管网络,并使用成像和其他测定,确定微血管网络的影响。
基于图像的端点上的脉管系统。第三,作为一项试点转化研究,我们将开发针对患者的
μ PTM(n=10),并将这些类器官中的氟脱氧葡萄糖(FDG)代谢活性与
来自临床FDG-PET的生物标志物。总之,该项目将提高研究人员的运行能力,
临床试验“芯片”,使用患者自己的肿瘤和临床批准的放射性药物。
最终,这些进展可以被转化为预测新药的疗效,测试生物学假设,
并对患者进行个性化治疗。
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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Guillem Pratx其他文献
Guillem Pratx的其他文献
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{{ truncateString('Guillem Pratx', 18)}}的其他基金
Investigation of nanobubble nucleation by radiation therapy
放射治疗纳米气泡成核的研究
- 批准号:
10642367 - 财政年份:2023
- 资助金额:
$ 52.99万 - 项目类别:
A Novel Assay to Individualize Resensitization of Iodine-Refractory Thyroid Cancer
碘难治性甲状腺癌个体化再敏化的新方法
- 批准号:
10612661 - 财政年份:2023
- 资助金额:
$ 52.99万 - 项目类别:
Tumor-targeted delivery and cell internalization of theranostic gadolinium nanoparticles for image-guided nanoparticle-enhanced radiation therapy
用于图像引导纳米颗粒增强放射治疗的治疗诊断钆纳米颗粒的肿瘤靶向递送和细胞内化
- 批准号:
10457237 - 财政年份:2019
- 资助金额:
$ 52.99万 - 项目类别:
High-throughput radionuclide counting and sorting of single cells
单细胞的高通量放射性核素计数和分选
- 批准号:
8850698 - 财政年份:2015
- 资助金额:
$ 52.99万 - 项目类别:
Real-time tracking of single cells in live animals
实时追踪活体动物的单细胞
- 批准号:
8930185 - 财政年份:2014
- 资助金额:
$ 52.99万 - 项目类别:
Quantitative Imaging of Cancer Drug Resistance via Radioluminescence Microarrays
通过放射发光微阵列对癌症耐药性进行定量成像
- 批准号:
8674402 - 财政年份:2014
- 资助金额:
$ 52.99万 - 项目类别:
Quantitative Imaging of Cancer Drug Resistance via Radioluminescence Microarrays
通过放射发光微阵列对癌症耐药性进行定量成像
- 批准号:
9477626 - 财政年份:2014
- 资助金额:
$ 52.99万 - 项目类别:
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