Nanodisc Platform for 19F-MRI
Nanodisc Platform for 19F-MRI
批准号:
10746675
负责人:
Nicholas Oliver Fischer
金额:
$27.29万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-07-11 至 2025-06-30
关键词:
AffectAnimalsApolipoproteinsAreaBiodistributionBiologicalBiological MarkersBiopsyBreast Cancer ModelCell Culture TechniquesCell TherapyCellsCharacteristicsChargeCholesterolCirculationClinicalComplexContrast MediaDetectionDevelopmentDiameterDimensionsDiseaseDisease MarkerDrug Delivery SystemsEnvironmentFluorineFluorocarbonsFormulationFoundationsGadoliniumGoalsHepatocyteHigh Density LipoproteinsHistologyHydrophobicityImageImmuneImmunologic SurveillanceInvestigationLabelLipid BilayersLipidsLiquid substanceLiverLongitudinal StudiesMacrophageMagnetic Resonance ImagingMembraneMethodsMicrofluidicsModalityModelingMonitoring Clinical TrialsMusNoiseOilsPhagocytesPhagocytosisPositioning AttributePrecision therapeuticsProductionProtonsRadiation therapyRadioisotopesReagentReticuloendothelial SystemRiskSamplingScaffolding ProteinSignal TransductionSpecificityStructureSurfaceSystemT-LymphocyteTechniquesTechnologyTestingTherapeuticThickTissuesToxic effectToxicity TestsTumor MarkersTumor-associated macrophagesVaccinesValidationWaterWorkaqueouscellular imagingchelationclinical imagingdetection sensitivitydisease diagnosisfluorophoreimaging agentimaging biomarkerimaging probeimaging studyimprovedinnovationinterestmanufacturing scale-upmimeticsmolecular imagingmouse modelnanodisc technologynanodisknanoemulsionnanomaterialsnanoparticlenanosystemsnew technologynovelnuclear imagingparticlephysical propertypilot testscale upspecific biomarkersstoichiometrysuccesssurfactanttargeted biomarkerultrasounduptake
中文摘要
19F核磁共振成像,在监测细胞治疗的临床试验中显示出有希望的成功
英文摘要
19F MRI, has shown promising success in clinical trials for monitoring cell therapy, where small groups of
cells, showing poor contrast in 1H-MRI (Magnetic Resonance Imaging), are easily tracked using 19F-MRI.1
Contrast is provided by nanoemulsions of perfluorocarbon (PFC) oils pre-loaded into cells. A major advantage
of 19F-MRI is that lack of natural fluorine in the body allows for very high contrast-to-noise for 19F-MRI
compared to 1H-MRI.2 Use of 19F-MRI in molecular imaging, by targeting specific biomarkers, is of great
interest, but the development of probes for these applications has been an elusive goal. Typical synthetic
methods produce relatively large particles, > 150 nm, which induce nonspecific uptake by phagocytic cells.
While avid nonspecific uptake is advantageous for labeling T cells and other immune cells ex vivo, it is a
decided limitation for imaging of biomarkers as it can create high background signal in the inflamed tissues
characteristic in many diseases. 19F MRI should be an excellent platform for biomarker detection but there is a
critical unmet need for suitable 19F MRI contrast agents that avoid nonspecific immune cell surveillance.
Ideally, contrast agents need to be<100 nm to avoid nonspecific uptake. We propose exploratory studies to
develop innovative new 19F MRI contrast agents based on nanodiscs. Nanodiscs are < 50 nm in size, avoid
liver clearance, and escape immune surveillance. We hypothesize that nanodiscs, which are structurally similar
to high density lipoproteins that carry cholesterol in a hydrophobic core, may be ideal for carrying hydrophobic
perfluorocarbons. Our aims are to explore synthetic parameters in benchtop (Aim 1) and microfluidic (Aim 2)
approaches to optimize loading of perfluorocarbons into nanodiscs. In each aim we will systematically
investigate variables that influence nanodisc size and perfluorocarbon loading. New nanodiscs will be
characterized for physical properties such composition and dimensions, and the top 3 products from each Aim
will be evaluated for lack of toxicity and biodistribution in a mouse model. The leading nanodiscs will be
modified for targeting CD204, a biomarker for tumor associated macrophages, and tested in a mouse breast
cancer model. We are team composed of contrast agent (UCD) and nanodisc (LLNL) experts who are ideally
positioned and well-equipped to carry out the proposed aims. The success of this project would add novel
nanodiscs materials with the potential not only for targeted 19F MR molecular imaging, but for applications in
photoacoustic, and radiotherapy, and tracking drug delivery.
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