FDG-PET imaging of pulmonary vascular remodelling in PAH
File(s)
Author(s)
Wang, Lei
Type
Thesis
Abstract
Pulmonary artery hypertension (PAH) is a disease of progressive pulmonary vascular remodelling characterised by dysregulated proliferation and inflammation. With increasing acceptance that glucose metabolism is perturbed in proliferating and inflammatory cells in PAH, the present thesis took interest in the application of molecular 18F-2-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) imaging, widely used in the oncology clinic, in the assessment of PAH patients. Our hypothesis is that FDG-PET imaging can be used as a potential tool for the in vivo assessment of pulmonary vascular remodelling and evaluation of anti-remodelling therapies in PAH.
In the first part of the thesis, a clinical applicable dynamic FDG-PET acquisition protocol with kinetic Patlak analysis was assessed in idiopathic PAH (IPAH) patients and PAH associated with systemic lupus erythematosus (SLE-PAH) patients for detection and quantification of lung FDG uptake. Mean lung FDG uptake was increased in both IPAH and SLE-PAH patients compared to that in healthy controls. There was heterogeneity of lung FDG uptake within PAH population, which aligns with our current understanding of the complex and regional pathology in PAH. Lung FDG uptake of SLE-PAH patients significantly correlated with SLE disease activity markers. In the following in vivo FDG-PET study, treatments with liraglutide and tacrolimus significantly attenuated the increased pulmonary artery pressure and right heart hypertrophy, as well as pulmonary vascular muscularisation and inflammatory cell infiltration in monocrotaline-induced PAH rat models, accompanied by a decreased lung FDG uptake. These data support further evaluation of the use of FDG-PET as a potential tool for evaluating these therapies in clinical trials.
We learnt that FDG-PET imaging lacks specificity to differentiate proliferation from inflammation as an underlying disease process. Future development of other PET tracer may help to identify a marker that interrogates the pulmonary pathology of interest.
In the first part of the thesis, a clinical applicable dynamic FDG-PET acquisition protocol with kinetic Patlak analysis was assessed in idiopathic PAH (IPAH) patients and PAH associated with systemic lupus erythematosus (SLE-PAH) patients for detection and quantification of lung FDG uptake. Mean lung FDG uptake was increased in both IPAH and SLE-PAH patients compared to that in healthy controls. There was heterogeneity of lung FDG uptake within PAH population, which aligns with our current understanding of the complex and regional pathology in PAH. Lung FDG uptake of SLE-PAH patients significantly correlated with SLE disease activity markers. In the following in vivo FDG-PET study, treatments with liraglutide and tacrolimus significantly attenuated the increased pulmonary artery pressure and right heart hypertrophy, as well as pulmonary vascular muscularisation and inflammatory cell infiltration in monocrotaline-induced PAH rat models, accompanied by a decreased lung FDG uptake. These data support further evaluation of the use of FDG-PET as a potential tool for evaluating these therapies in clinical trials.
We learnt that FDG-PET imaging lacks specificity to differentiate proliferation from inflammation as an underlying disease process. Future development of other PET tracer may help to identify a marker that interrogates the pulmonary pathology of interest.
Version
Open Access
Date Issued
2016-02
Date Awarded
2016-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Zhao, Lan
Wilkins, Martin
Publisher Department
Department of Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)