Quantifying 18kDa TSPO Expression in the Lung in Pulmonary Artery Hypertension (PAH)
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 requirements
Exclusion Criteria:
Unable to provide informed consent and/or are non-fluent speakers of the English language
TT Genotype at the rs6971 locus
Clinically-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/dl
Sickle cell disease or thalassaemia
History of uncontrolled systemic hypertension
Acute infection (including eye, dental, and skin infections)
Chronic inflammatory disease including HIV, and Hepatitis B
Women of childbearing potential who are pregnant or breastfeeding
Patients 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 visit
Participation in a research study involving significant ionisation radiation within the last 3 years
Significant radiation exposure other than dental X-rays in last 1 year
Positive Allen's test.
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