Optimization of PET probe for imaging lung fibrogenesis
Optimization of PET probe for imaging lung fibrogenesis
批准号:
10054488
负责人:
Peter D Caravan
金额:
$58.8万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-08-15 至 2022-07-31
关键词:
AddressAffinityAldehydesAnimal ModelAreaBindingBiochemicalBiological AssayBiopsyBleomycinBlood VesselsBlood specimenCicatrixClinicalClinical TrialsCollagenDetectionDevelopmentDiagnosisDiseaseDisease ProgressionDoseDrug KineticsEarly DiagnosisEarly treatmentFibrosisFundingGoalsHandHeartHepatobiliaryHigh Resolution Computed TomographyHumanImageImaging DeviceIn VitroIndividualIndolesInflammatoryLOX geneLabelLeadLibrariesLiverLiver FibrosisLungMagnetic ResonanceMeasuresMetabolicMetabolismMethodsModelingMolecularMolecular ProbesMonitorMusNatural HistoryOxidesPathogenicityPatient CarePatientsPharmacotherapyPhasePositron-Emission TomographyPropertyPulmonary FibrosisPulmonary function testsRattusReportingRespiratory physiologySelection for TreatmentsSerumSignal TransductionSpecificityStructure of parenchyma of lungTimeTissuesTracerTranslatingWorkanatomic imagingclinical developmentclinical translationdesigndrug developmentfibrogenesishydrophilicityidiopathic pulmonary fibrosisimaging probeimprovedin vivoindium-bleomycininhibitor/antagonistinjuredlead optimizationlead serieslung imaginglung injurylung lobemolecular imagingmouse modelnonhuman primateoptimal treatmentsquantitative imagingstandard of caretreatment responseuptake
中文摘要
项目总结/文摘
英文摘要
Project Summary/Abstract
The goal of this project is to optimize a positron emission tomography (PET) probe to quantify fibrogenesis
(active disease) in the lung to ultimately provide an early diagnosis of idiopathic pulmonary fibrosis (IPF), to
predict disease progression, and to provide an early indication of whether anti-fibrotic therapy is likely to be
effective. IPF is a progressive and ultimately fatal disease with a median survival of less than 4 years from the
time of diagnosis. The treatment options remain limited due to highly variable clinical course and poorly
understood pathogenic mechanisms. Current strategies to diagnose and monitor IPF include lung biopsy,
pulmonary function tests that measure global lung function, and anatomic imaging tools such as high-resolution
computed tomography (HRCT). Yet these methods are limited in their ability to detect disease early, determine
disease activity at any one measure, or monitor the therapeutic response. Our group recently demonstrated that
oxidized collagen is a marker of active disease in pulmonary fibrosis. In animal models, using molecular probes
that target the allysine residue on oxidized collagen, we showed that a molecular probe targeted to allysine could
detect fibrogenesis, monitor treatment response and could distinguish active fibrogenesis from stable scar in
models of lung fibrosis. We further showed that by modifying the affinity and reactivity (on-rate), that probe uptake
in areas of active disease could be increased in a rational manner.
In this Catalyze: Preliminary Product/Lead Series Identification proposal, we aim to optimize our lead PET
probe with respect to its uptake in areas of disease and its elimination from non-diseased lung and surrounding
tissues, thus providing a very high target to background ratio and enabling accurate quantification of lung
fibrogenesis. With the optimized probe in hand, we will then demonstrate its efficacy in different animal models
of pulmonary fibrosis, demonstrate its specificity to quantify active disease, and show that it can monitor
treatment response. At the end of this two year project we will have an optimized and validated PET probe for
imaging lung fibrogenesis and be poised to translate this probe to human clinical trials.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Inductively Coupled Plasma Mass Spectrometer
-
批准号:10412417
-
项目类别:
-
资助金额:$59.84万
-
财政年份:2022
-
负责人:Peter D Caravan
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依托单位:
PET-MR Imaging of pulmonary fibrosis
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批准号:10430239
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项目类别:
-
资助金额:$82.66万
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财政年份:2021
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负责人:Peter D Caravan
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依托单位:
PET-MR Imaging of pulmonary fibrosis
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批准号:10654552
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项目类别:
-
资助金额:$82.42万
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财政年份:2021
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负责人:Peter D Caravan
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依托单位:
PET-MR Imaging of pulmonary fibrosis
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批准号:10298635
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项目类别:
-
资助金额:$82.97万
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财政年份:2021
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负责人:Peter D Caravan
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依托单位:
Molecular MR Imaging of Hepatic Fibrogenesis
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批准号:10408068
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项目类别:
-
资助金额:$66.1万
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财政年份:2019
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负责人:Peter D Caravan
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依托单位:
The Future of Molecular MR: A Cellular and Molecular MR Imaging Workshop
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批准号:9763108
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项目类别:
-
资助金额:$1.6万
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财政年份:2019
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负责人:Peter D Caravan
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依托单位:
Molecular MR Imaging of Hepatic Fibrogenesis
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批准号:10360979
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项目类别:
-
资助金额:$13.11万
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财政年份:2019
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负责人:Peter D Caravan
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依托单位:
PET Imaging of Pulmonary Fibrosis
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批准号:9090458
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项目类别:
-
资助金额:$76.93万
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财政年份:2016
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负责人:Peter D Caravan
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依托单位:
Molecular Imaging of Renal Fibrogenesis
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批准号:8824746
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项目类别:
-
资助金额:$38.24万
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财政年份:2014
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负责人:Peter D Caravan
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依托单位:
Molecular Imaging of Renal Fibrogenesis
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批准号:9352722
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项目类别:
-
资助金额:$1.07万
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财政年份:2014
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负责人:Peter D Caravan
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依托单位:
Molecular Imaging of Renal Fibrogenesis
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批准号:9120677
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项目类别:
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资助金额:$38.24万
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财政年份:2014
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负责人:Peter D Caravan
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依托单位:
Molecular Imaging of Renal Fibrogenesis
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批准号:9916559
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项目类别:
-
资助金额:$15.0万
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财政年份:2014
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负责人:Peter D Caravan
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依托单位:
HPLC-ICP-MS System
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批准号:8447659
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项目类别:
-
资助金额:$37.12万
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财政年份:2013
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负责人:Peter D Caravan
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依托单位:
PET Imaging of Pulmonary Fibrosis
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批准号:8416813
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项目类别:
-
资助金额:$43.49万
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财政年份:2012
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负责人:Peter D Caravan
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依托单位:
PET Imaging of Pulmonary Fibrosis
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批准号:8550816
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项目类别:
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资助金额:$41.37万
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财政年份:2012
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负责人:Peter D Caravan
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依托单位:
PET Imaging of Pulmonary Fibrosis
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批准号:8681509
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项目类别:
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资助金额:$42.44万
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财政年份:2012
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负责人:Peter D Caravan
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依托单位:
PET Imaging of Thrombus
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批准号:10365099
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项目类别:
-
资助金额:$80.41万
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财政年份:2011
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负责人:Peter D Caravan
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依托单位:
Activatable MR Imaging Probes
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批准号:8329619
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项目类别:
-
资助金额:$28.91万
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财政年份:2011
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负责人:Peter D Caravan
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依托单位:
High throughput assay for fibrin-binding probes
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批准号:8182040
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项目类别:
-
资助金额:$17.7万
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财政年份:2011
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负责人:Peter D Caravan
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依托单位:
PET Imaging of Thrombus
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批准号:8703166
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项目类别:
-
资助金额:$72.01万
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财政年份:2011
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负责人:Peter D Caravan
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依托单位:
海外基金