An open-label, multi-tracer, imaging study to evaluate and compare Positron Emission Tomography (PET) tracers targeting Collagen Type I and Fibroblast Activation Protein (FAP) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and healthy volunteers
Metabolic dysfunction-associated steatotic liver disease (MASLD), with a specific focus on active liver fibrogenesis (tissue remodelling and the deposition of extracellular matrix/scar tissue
This open-label study spans a maximum 8.5-month period per participant, consisting of two screening visits, up to two dynamic PET imaging sessions, and a final follow-up safety phone call 4–7 days post-imaging. Screening and Baseline: Participants undergo multi-modality liver MRI sequences on a 3 Tesla clinical system during the screening window to establish structural baselines, liver stiffness via Magnetic Resonance Elastography (MRE), and liver fat via proton density fat fraction (MRI-PDFF). Imaging Sessions: Enrolled participants attend up to two distinct PET imaging sessions separated by a washout period of at least 7 days (and up to 6 months). For logistical convenience, the administration order of the two novel tracers can be interchanged across the sessions. No participant will exceed 2 total PET scans throughout the trial. Scanner Parameters: All molecular imaging is performed at a single site using a Siemens Biograph Horizon 16 4R PET/CT scanner. Step-by-Step Scan Interventions 1. Anatomical Localisation: Immediately prior to radiotracer administration, a brief, low-dose CT scan is performed on the participant for anatomical localization and radiation attenuation correction. 2. Tracer Administration: Simultaneously with the initiation of the dynamic PET emission scan, participants receive a single sub-pharmacological intravenous bolus microdose of one of two novel radiotracers: [68Ga]-CBP8 (targeting collagen type I); mass dose ≤ 100 µg, administered radioactivity ≤150 MBq. [18F]-LNTH-1363S (targeting fibroblast-activation protein); mass dose ≤ 100 µg, administered radioactivity ≤150 MBq. 3. Kinetic Sampling: To establish a tracer metabolite-corrected plasma input function and quantify parent tracer-related radioactivity over the course of the dynamic scan, intensive vascular blood sampling is performed. This is primarily achieved via a temporary radial artery cannula inserted under local anaesthesia after confirmation of collateral circulation pate
General Inclusion Criteria (All Participants) 1. Male or female volunteers 2. Agree to follow the contraception requirements of the study 3. Able to give fully informed written consent. Cohort Specific: Patients with MASLD (Cohort A) 1. Volunteers with a diagnosis of MASLD with F3–F4 liver fibrosis based on historic liver biopsy and non-invasive markers: liver stiffness with magnetic resonance elastography (MRE) ≥ 4.3 kPa 2. Alanine aminotransferase (ALT) > upper limit of normal (ULN) and < 5 × ULN 3. Liver fat content (magnetic resonance imaging-proton density fat fraction [MRI-PDFF]) > 10% 4. Body Mass Index (BMI) ≥ 25 kg/m2 5. registered with a general practitioner (GP) in the UK Cohort Specific: Healthy Volunteers (Cohort B) 1. Normotensive volunteers deemed healthy on the basis of a clinical history, medical examination, electrocardiogram (ECG), vital signs, and laboratory tests of blood and urine 2. Normal liver stiffness (MRE < 2.5 kPa) 3. BMI in the range 18.5–24.9 kg/m2 4. Liver fat content (MRI-PDFF) < 5%
All volunteers: 1. Positive tests for hepatitis B & C, human immunodeficiency virus (HIV) 2. Severe adverse reaction to any drug 3. History of malignancy or carcinoma in the last 5 years 4. History of liver transplant 5. Presence or history of drug or alcohol abuse 6. Drink more than 14 units of alcohol weekly 7. Smoke more than 10 cigarettes daily or heavy use of e-cigarettes 8. Use of high-dose corticosteroids from 3 months before the first PET scan until the end of the study 9. Participation in other clinical studies of unlicensed medicines, or loss of more than 400 mL of blood, within the 3 months before the first PET scan 10. Clinically relevant abnormal findings at the screening assessment, acute or chronic illness, or clinically relevant abnormal medical history or concurrent medical condition (unless resulting from MASH in Group 1) 11. Possibility that volunteer will not cooperate 12. Pre-menopausal females who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception 13. Unsatisfactory venous access 14. Significant exposure to ionizing radiation (more than 10 mSv) within the previous 12 months 15. Contraindications to arterial cannulation, magnetic resonance imaging (MRI), PET or computed tomography (CT) 16. Objection by General Practitioner (GP).