Proj 1: In Vivo Optical Molecular Imaging with Fluorescence Peptides
Proj 1: In Vivo Optical Molecular Imaging with Fluorescence Peptides
批准号:
7490304
负责人:
Thomas D Wang
金额:
$24.53万
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-04-01 至 2013-03-31
关键词:
3-DimensionalAffinityAnimal ModelAntibodiesArchitectureAreaBacteriophage M13BacteriophagesBindingBinding SitesBiological MarkersCDX2 geneCaliberCellsClinicClinicalColitisCollectionCollimatorColonColon CarcinomaColon, RectumColonic AdenomaColonoscopyColorectalCompatibleCultured CellsCustomDepthDetectionDevelopmentDimensionsDiseaseDistalDyesDysplasiaEndoscopesEndoscopyEngineeringEnzyme-Linked Immunosorbent AssayEpithelialEpitheliumExhibitsFluorescein-5-isothiocyanateFluorescenceGastrointestinal tract structureGenetically Engineered MouseGenus ColaGoalsHT29 CellsHistologyHumanIceImageImaging TechniquesIntestinesIonsIrrigationLabelLesionLibrariesLightLightingLocalizedLongitudinal StudiesMechanicsMediatingMedicalMethodologyMethodsMicroscopeMicroscopicModelingMolecular ProbesMonitorMucous MembraneNeoplasmsOpticsOrganPatientsPenetrationPeptidesPerformancePersonal SatisfactionPhage DisplayPolypsPre-Clinical ModelPremalignantPropertyPublic HealthRateReagentRecording of previous eventsResearchResectedResolutionRiskScanningScreening for cancerScreening procedureSiteSpatial DistributionSpecimenSpeedSurfaceSystemTechniquesTherapeuticTissuesTopical applicationToxic effectTransgenesTranslatingTranslationsValidationVisualization softwareWorkadenomabaseclinically significantcolon dysplasiacombinatorialdesignfluorescence imagingfluorescence microscopehuman subjectimage reconstructionimage visualizationimaging probeimmunogenicityimprovedin vivoinnovationinstrumentinstrumentationmicrobial alkaline proteinase inhibitormillimetermolecular imagingmouse modelnoveloptical imagingpolyposispre-clinicalpromoterprototyperecombinasesizetoolvalidation studies
中文摘要
项目1:本研究计划的长远目标是开发一种综合光学系统
英文摘要
PROJECT 1: The broad, long-term objectives of this research plan are to develop an integrated optical
molecular imaging strategy that uses fluorescence peptides as probes to target the presence of premalignant
(dysplastic) tissue in vivo. Macroscopic and microscopic fluorescence instruments are developed
as complementary imaging methods for peptide detection. This methodology can be used for monitoring
biomarker expression in small animal models and for the early detection of cancer in human patients undergoing
screening. In this application, the colonic adenoma is used as a model for dysplasia. The specific aims are to
1) identify 5 candidate peptides using techniques of phage display for biopanning against cultured cells and
freshly excised specimens of human colonic mucosa, 2) develop new optical imaging instrumentation using the
dual axes confocal architecture to visualize the tissue microarchitecture relevant to peptide binding, and 3)
validate preferential peptide binding to dysplasia in vivo in a genetically engineered mouse that forms polyps in
the distal colon by somatic activation of Cre-recombinase and in human subjects undergoing routine screening
colonoscopy. Peptides are chosen for development as probes because their high diversity and small size
can provide high affinity binding with deep tissue penetration, and their low risk of immunogenicity and
toxicity facilitate translation for use in the clinic. Phage display is a powerful combinatorial technique that
provides an unbiased approach for identifying unique peptides that exhibit affinity binding to dysplastic
mucosa as is well suited to accommodate subtle changes associated with the in vivo microenvironment. The
dual axes confocal architecture provides an instrument that can achieve sub-cellular resolution with long
working distance and overcomes the effects of tissue scattering using off-axis fluorescence collection.
Moreover, this design can be scaled down in size for endoscope compatibility. A 5 mm diameter instrument
package is sufficiently small to pass through a 6 mm diameter instrument channel in a therapeutic endoscope.
High speed scanning is performed with a tiny MEMS (micro-electro-mechanical systems) mirror that collects
optical sections at a sufficient frame rate for generating 3D volumetric images. The candidate peptides will be
topically applied to colonic adenomas and surrounding normal appearing mucosa followed by macroscopic
fluorescence imaging to localize regions of increased peptide binding for subsequent microscopic fluorescence
imaging to assess the spatial distribution of peptide binding within the dysplastic crypt microarchitecture.
Public Health: The proposed studies will result in the development of novel optical imaging probes and
instruments that can be evaluated in pre-clinical models as well as translated to the clinic as practical
screening tool for the early detection of cancer in hollow organs.
期刊论文(0)
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科研奖励(0)
会议论文
Early detection of colorectal cancer in the traditional and serrated pathways
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批准号:10471944
-
项目类别:
-
资助金额:$33.83万
-
财政年份:2020
-
负责人:Thomas D Wang
-
依托单位:
Early detection of colorectal cancer in the traditional and serrated pathways
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批准号:10244933
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项目类别:
-
资助金额:$34.52万
-
财政年份:2020
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负责人:Thomas D Wang
-
依托单位:
Early detection of colorectal cancer in the traditional and serrated pathways
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批准号:9974634
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项目类别:
-
资助金额:$34.52万
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财政年份:2020
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负责人:Thomas D Wang
-
依托单位:
Early Detection of Colorectal Cancer on Near-Infrared Molecular Endoscopy
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批准号:9922878
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项目类别:
-
资助金额:$43.72万
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财政年份:2016
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负责人:Thomas D Wang
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依托单位:
Early Detection of Colorectal Cancer on Near-Infrared Molecular Endoscopy
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批准号:9030043
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项目类别:
-
资助金额:$40.32万
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财政年份:2016
-
负责人:Thomas D Wang
-
依托单位:
Multiplexed Multi-Modal Endoscopic Imaging of Cancer Biomarkers
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批准号:8890458
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项目类别:
-
资助金额:$35.87万
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财政年份:2015
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负责人:Thomas D Wang
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依托单位:
Project 2: Peptide imaging agents for early targets in progression from BE to EAC
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批准号:10268346
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项目类别:
-
资助金额:$23.05万
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财政年份:2011
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负责人:Thomas D Wang
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依托单位:
Administrative Core
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批准号:10155437
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项目类别:
-
资助金额:$27.11万
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财政年份:2011
-
负责人:Thomas D Wang
-
依托单位:
Administrative Core
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批准号:8244094
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项目类别:
-
资助金额:$19.02万
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财政年份:2011
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负责人:Thomas D Wang
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依托单位:
Targeted Peptide Selection and Validation
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批准号:8555331
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项目类别:
-
资助金额:$21.31万
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财政年份:2011
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负责人:Thomas D Wang
-
依托单位:
Project 2: Peptide imaging agents for early targets in progression from BE to EAC
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批准号:10155439
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项目类别:
-
资助金额:$31.68万
-
财政年份:2011
-
负责人:Thomas D Wang
-
依托单位:
Administrative Core
-
批准号:8555333
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项目类别:
-
资助金额:$19.4万
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财政年份:2011
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负责人:Thomas D Wang
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依托单位:
Targeted Peptide Selection and Validation
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批准号:8244089
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项目类别:
-
资助金额:$22.62万
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财政年份:2011
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负责人:Thomas D Wang
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依托单位:
In Viro Detection of Neoplasia in the Digestive Tract
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批准号:8132375
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项目类别:
-
资助金额:$95.07万
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财政年份:2008
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负责人:Thomas D Wang
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依托单位:
In Viro Detection of Neoplasia in the Digestive Tract
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批准号:7692935
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项目类别:
-
资助金额:$120.0万
-
财政年份:2008
-
负责人:Thomas D Wang
-
依托单位:
In Viro Detection of Neoplasia in the Digestive Tract
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批准号:7560898
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项目类别:
-
资助金额:$105.0万
-
财政年份:2008
-
负责人:Thomas D Wang
-
依托单位:
In Viro Detection of Neoplasia in the Digestive Tract
-
批准号:7929607
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项目类别:
-
资助金额:$118.83万
-
财政年份:2008
-
负责人:Thomas D Wang
-
依托单位:
Administrative Core
-
批准号:7728723
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项目类别:
-
资助金额:$4.24万
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财政年份:2008
-
负责人:Thomas D Wang
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依托单位:
Primary Project 1
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批准号:7728712
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项目类别:
-
资助金额:$33.75万
-
财政年份:2008
-
负责人:Thomas D Wang
-
依托单位:
In Viro Detection of Neoplasia in the Digestive Tract
-
批准号:8324711
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项目类别:
-
资助金额:$85.07万
-
财政年份:2008
-
负责人:Thomas D Wang
-
依托单位:
海外基金