Validation of the Analysis Methodology Behind the Use of Quantitative 18F-FDG PET/CT to Assess Lung Inflammation

For patients with sarcoidosis: Inclusion Criteria:

• Suspected pulmonary sarcoidosis (as determined by referring physician)

• Requires bronchoscopy, EBUS and BAL (as determined by ILD team at Royal Papworth orAddenbrooke's Hospitals).

• Male or female ≥ 30 years with a BMI of 17-35kg/m2

• Consents to additional bronchoscopic evaluation during NHS mandated bronchoscopy, EBUSand BAL.

Exclusion Criteria:

• Inability to provide Informed Consent.

• A cardiovascular event in the last 6 months (i.e. acute coronary syndrome, unstableangina, CABG, PCI, stroke, MI, carotid endarterectomy).

• Patients with known clinically significant pulmonary diagnoses of COPD, lung fibrosis,interstitial lung disease, or α1-antitrypsin deficiency.

• Active smoking during the last 5 years.

• Patients with known chronic infections such as HIV or known active tuberculosis.

• Patients with rheumatoid arthritis, connective tissue disorders and other conditionsknown to be associated with active chronic inflammation (e.g. Inflammatory BowelDisease).

• Known diabetes mellitus or known impaired glucose tolerance

• Participation in a previous research trial in the last three years which involvedexposure to significant ionising radiation (i.e. cumulative research radiation dose >10 mSv)

• Pregnancy

• Women of childbearing potential [i.e. either postmenopausal or documented hysterectomyand/or bilateral oophorectomy - tubal ligation is not sufficient].

• Use of systemic steroids (oral or intravenous) at a dose > 10mg od of prednisolone orequivalent and/or antibiotics 4 weeks prior to PET/CT scan

• Any medical history or clinically relevant abnormality that is deemed by the principalinvestigator and/or medical monitor to make the subject ineligible for inclusionbecause of a safety concern For healthy volunteers: Inclusion criteria:

• Age/gender-matched group (Part A only): Male or female ≥ 30 years with a BMI of 17-35kg/m2 inclusive

• LPS/saline challenge group (Part B only): Male or female ≥ 50 years with a BMI of 17-35kg/m2 inclusive

• No smoking history

• Normal predicted spirometry values: FEV1/FVC > 0.7 and FEV1 > 80% predicted

• Healthy as determined by clinical history & examination by the investigator Exclusion criteria:

• Inability to provide informed consent

• Pregnancy

• Patients with known chronic inflammation conditions such as rheumatoid arthritis,connective tissue disorders and inflammatory bowel disease

• A significant cardiovascular event in the last 6 months

• Insulin dependent diabetes mellitus or known impaired glucose tolerance

• Participation in previous research trial in the last three years which involvesexposure to significant ionising radiation (cumulative dose >10mSv)

• Use of systemic steroids (oral or intravenous) at a dose > 10mg od of prednisolone orequivalent and/or antibiotics 4 weeks prior to PET/CT scan

• Any medical history or clinically relevant abnormality that is deemed by the principalinvestigator and/or medical monitor to make the subject ineligible for inclusionbecause of a safety concern

• Women of childbearing potential

• Patients with known chronic infections such as HIV or known active tuberculosis.

• Active smoking history (defined as > than 1 cigarette per day on a regular basis) overlifetime

• Known lung and/or respiratory disease or associated symptoms (e.g. dyspnoea, wheeze)