Page 145 - Assessing right ventricular function and the pulmonary circulation in pulmonary hypertension Onno Anthonius Spruijt

the natural history of the vascular pathology of IPAH; for example, it could be episodic with periods of vascular proliferation interspersed and with periods of relative quiescence, or vascular remodeling could be an early event with little cellular activity during the later stages of the disease. A cross sectional study of IPAH patients would be expected to reflect this variation. Furthermore, we analysed data by 3‐dimensional parametric mapping of computed per‐voxel 18FLT uptake. There was an uneven pattern of 18FLT signal distribution within the lungs of severe disease, which may report the patchy distribution of the vascular pathology within the lung, as seen on histological examination [4,6]. This variability is likely to explain the absence of an association between overall lung 18FLT phosphorylation, k3, and mean pulmonary artery pressure or pulmonary vascular resistance in this small cohort of IPAH patients.
Results from pre‐clinical animal studies and clinical oncology investigations indicate that 18FLT PET could be a useful biomarker for measuring the difference in tumour growth rates in the course of therapy. Our data from the MCT rat model of PAH showed an association between increased lung 18FLT uptake and the progression of pulmonary vascular remodelling. The remodelled vessels in the MCT rat lung demonstrated increased Ki‐67 expression as well as prominent thymidine kinase TK1 and transporter ENT1 expression. 18FLT phosphorylation, k3, levels were also increased in proportion to peripheral pulmonary vascular muscularization and the proliferation Ki‐67 score. Treatment with DCA and imatinib in the MCT model attenuated pulmonary hypertension and vascular remodelling, reduced the disease‐driven increase in lung TK1 and ENT1 expression, and the 18FLT PET lung signal was reduced in line with decreased peripheral vascular muscularization. Our data suggests that 18FLT PET may be a useful tool to assess response to treatment in patients with PAH.
Conclusions
The present study demonstrates the potential of dynamic 18FLT PET imaging to report on the vascular pathology in IPAH. We suggest that, given the variability in uptake between patients, it might be a useful tool for identifying patients who might benefit most from anti‐proliferative therapy and so support precision medicine. The value of 18FLT PET as a tool in evaluating therapeutic strategies targeted at resolving pulmonary vascular remodelling in the clinic merits further study.
Sources of Funding
Chapter 8
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