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

Summary

The purpose of this study is to validate the method of analysing Positron Emission Tomography (PET) images to assess lung inflammation. Development of novel therapeutic drugs requires a biomarker which is sensitive to the underlying disease and can respond to therapeutic interventions. PET is a potential imaging biomarker which can target molecular and cellular processes. There is currently no standardised method of analysing PET lung data and a lack of validation for the existing techniques.

This study is divided in to two parts. Part A aims to determine the best method to perform 18F-FDG PET/CT lung analysis and how it correlates with cell counts from bronchoalveolar lavage (BAL) samples taken from participants with active pulmonary sarcoidosis.

Part B will compare imaging data from healthy volunteers who have either undergone a Lipopolysaccharide (LPS) challenge (whereby the lung is temporarily inflamed) or saline equivalent to determine whether lung inflammation can be detected by 18F-FDG PET/CT. No medications will be given and patients will not be asked to stop or change existing medication.

Conditions

• Lung Inflammation
• Sarcoidosis

Interventions

RADIATION

PET/CT scan

PET/CT will be performed at Cambridge University Hospital's PET-CT unit, Cambridge. Participants in Part A of the study (sarcoidosis and HVs) will receive one PET/CT scan. A Cine-CT scan will be performed immediately prior to the 18F-FDG PET/CT scan. Settings for the CT scans will be determined by clinical protocols, radiation dose will be kept as low as reasonably practicable (ALARP) consistent with UK legislation. After 6 hours of fasting and if blood glucose concentration is ≤11mmol/L participants will proceed to undergo an 18FDG PET/CT scan. 18F-FDG will be administered intravenously at a dose of approximately 200 MBq. Positron emission scanning will involve a 60-minute dynamic acquisition from the lungs.

OTHER

LPS Challenge

In Part B, eight healthy volunteers will undergo an LPS challenge whereby each participant is injected with the challenge agent, Lipopolysaccharide (LPS), to invoke temporary mild lung inflammation. Each participant will have a PET/CT scan before and after the administration of LPS and the images will be assessed to determine whether these methods are able to detect true lung inflammation.

OTHER

Saline Challenge

In Part B, four healthy volunteers will undergo a saline challenge as outlined above for the LPS challenge. Pre- and post-challenge scans will provide control data for the study.

DIAGNOSTIC_TEST

Blood and urine sampling

For women whose post-menopausal status and/or pregnancy status is uncertain at screening, a blood sample will be collected to test for pregnancy and menopausal status (hormone profiling) before enrolling them on to the study. If pregnancy status is still uncertain at study visits, participants will have a urine pregnancy test before undergoing any PET/CT scans to ensure it is safe for them to continue in the study.

Sponsors & Collaborators

• GlaxoSmithKline

  collaborator INDUSTRY

• Cambridge University Hospitals NHS Foundation Trust

  lead OTHER

Principal Investigators

• Joseph Cheriyan, MBChB, MA, FRCP · Cambridge University Hospitals NHS Foundation Trust

Eligibility

Min Age

30 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-01-23

Primary Completion

2022-01-31

Completion

2022-01-31

Countries

• United Kingdom

Study Locations