Quantifying 18kDa TSPO Expression in the Lung in Pulmonary Artery Hypertension (PAH)

The aim of this study is to determine whether there is an increase in the TSPO PET signal (measured with the radioligand [11C]PBR28) in the lungs of patients living with PAH relative to age matched controls. If so, TSPO PET may be a useful technique to non-invasively monitor response to therapy. To do this, we will perform 2 [11C]PBR28 PET scans. The first will quantify the total [11C]PBR28 PET signal. This signal is a combination of the specific signal (VS) and the nonspecific signal (VND). The second scan will be performed following dosing with an unlabelled TSPO ligand. By directly measuring the total [11C]PBR28 signal (scan 1) and the nonspecific [11C]PBR28 signal (scan 2) we can therefore calculate the specific [11C]PBR28 signal, and hence the amount of TSPO in the lung.

Inclusion Criteria:Able to provide written informed consent prior to any study mandated procedures.Able to lie comfortably on back for up to 90 minutes at a time.Fertile females (women of childbearing potential) are eligible to participate after a negative highly sensitive pregnancy test, if they are taking a highly effective method of contraception other than the oral contraceptive pill until the end of relevant systemic exposure.Male participants who are fertile are eligible to participate if they are willing to comply with the contraceptive requirementsExclusion Criteria:Unable to provide informed consent and/or are non-fluent speakers of the English languageTT Genotype at the rs6971 locusClinically-significant renal disease (confirmed by creatinine clearance <30 ml/min per 1.73m2)Clinically-significant liver disease (confirmed by serum transaminases >2 times than upper normal limit)Anaemia confirmed by haemoglobin concentration <10 g/dlSickle cell disease or thalassaemiaHistory of uncontrolled systemic hypertensionAcute infection (including eye, dental, and skin infections)Chronic inflammatory disease including HIV, and Hepatitis BWomen of childbearing potential who are pregnant or breastfeedingPatients who have received an Investigational Medicinal Product (IMP) within 5 half-lives of the last dose of the IMP or 1 month (which ever is greater) before the baseline visitParticipation in a research study involving significant ionisation radiation within the last 3 yearsSignificant radiation exposure other than dental X-rays in last 1 yearPositive Allen's test.-