Gallium 68 Tilmanocept for PET Imaging of Atherosclerosis Plaques

Myocardial infarctionsMIor heart attacksischemic strokesISand peripheral artery diseasePADtogether considered cardiovascular diseaseCVDare all commonly caused by the same underlying pathologyatherosclerosisMIs and ISs are the leading causes of death and disability worldwideAtherosclerosis is a progressive pathology that develops asymptomatically over the course of many years as inflammatory plaques in the walls of arteriesEventual ruptures of atherosclerotic plaques result in blood clotsblocking blood flow and causing infarctionsi eCVD eventsInflammatory plaques that are most likely to rupture are currently challenging to detect and characterize without invasive proceduresCurrently available non invasive imaging modalities for atherosclerosis lack sensitivity and or specificity for inflammatory plaquesThere is great need for a non invasive imaging modality that can specifically detect inflammatory atherosclerotic plaques with high sensitivitySuch an imaging modality would enable more accurate identification of individuals at high risk for experiencing a first major CVD eventMI or ISand would facilitate monitoring of atherosclerosis directed therapies and life style modificationAchieving these benefits would meaningfully reduce the catastrophic toll that is inflicted upon our society by atherosclerosis mediated CVD eventsTo address this unmet needNavidea and the University of Alabama BirminghamUABare collaborating to develop GalliumGalabelled tilmanocept as a radiopharmaceutical positron emission tomographyPETimaging agent for inflammatory atherosclerotic plaquesTilmanocept is a synthetic ligand for the macrophage mannose receptorCDwithDTPA moieties that enable labeling withGaCDmacrophages are highly numerous in inflammatory plaques but not in plaques with resolved inflammation or uninvolved relevant tissueThe hypothesis of this proposal is that intravenouslyIVinjectedGa tilmanocept will localizes specifically to inflammatory plaques and permit sensitive quantitative imaging with PETTo test this hypothesiswe propose to evaluateGa tilmanocept PET imaging in the ApoE mouse model of atherosclerosisIncluding appropriate controlsa total ofmice will be evaluatedIn this modelinflammatory atherosclerotic plaques develop along the aortas of the miceAnimals will be injected IV withGa tilmanocept and imaged to quantitatively determine sites ofGa tilmanocept localizationThe animals will then be euthanized after which their aortas will be dissected and subjected to autoradiographyAreas of varying degrees of localization will be identified and processed for immunoflorescentIFevaluation with anti CDantibodies and the murine macrophage marker FQuantitative assessments of CDand Fexpression will be compared to each other and to the degree ofGa tilmanocept localization as determined by PET and autoradiographyThese comparisons with determine the correlation between CDexpression andGa tilmanocept localization and will confirm that CDexpression is largely restricted to macrophages in inflammatory plaquesThese experiments will establish the feasibility ofGa tilmanocept based PET imaging to specifically identify inflammatory plaques and provide the foundation for further studies developingGa tilmanocept PET as a non invasive atherosclerosis imaging modality in human subjects This project seeks to develop a galliumGalabeled radiopharmaceutical diagnostic imaging agentGa tilmanoceptfor positron emission tomographyPETimaging of atherosclerotic plaques in the walls of arteries and characterization of their inflammatory microenvironmentsThis project will enable improved risk assessment and monitoring of therapies for individuals at risk for myocardial infarctionsheart attacksand ischemic strokesthe leading causes of death worldwideIf successfulthis project will significantly reduce the catastrophic burdens inflicted upon our society by these conditions