FAPI PET Imaging - An Exploratory Study

Overview

This study is testing a new imaging tracer called \[18F\]FAPI-74 with PET scans. Researchers want to find out how well this tracer shows certain diseases in the body, including several types of cancer and some non-cancer conditions like fibrosis and sarcoidosis. \[18F\]FAPI-74 attaches to a protein found on cells that are active in tumors and areas of scarring or inflammation. This may help doctors see these areas more clearly than with imaging methods used today, especially in diseases where current scans do not work well. People who join this study will get one injection of the tracer into a vein, then have one PET/CT or PET/MR scan. This takes about 2 hours in total. Researchers will compare the results with imaging the participant already had as part of their regular care, such as other PET scans, CT, or MRI. No extra treatment is given, and no other visits are needed. The study will take place at 5 hospitals in Switzerland and plans to include about 770 adults with a confirmed or suspected diagnosis of one of the conditions being studied. The main goal is to see how clearly the tracer shows up on the scan. Researchers will also look at whether this new scan changes how confident doctors feel about a diagnosis, or changes the patient's treatment plan.

Background and Rationale: Fibroblast Activation Protein (FAP) is highly expressed in cancer-associated fibroblasts and in a range of fibrotic and inflammatory diseases. \[18F\]FAPI-74 is a novel PET radiotracer that binds selectively to FAP, enabling visualization of fibroblast activity. Early clinical studies have demonstrated promising tumour-to-background contrast, superior detectability compared with FDG in several tumours, and potential value in diseases where no adequate PET tracers exist. This multicentre study aims to systematically evaluate biodistribution, uptake patterns, and diagnostic usefulness of \[18F\]FAPI-74 across a broad spectrum of oncologic and non-oncologic indications. Study Design: This is an open-label, non-randomized, single-arm, exploratory diagnostic study conducted at five Swiss centres. Each participant undergoes a single administration of \[18F\]FAPI-74 followed by one PET/CT or PET/MR scan. No therapeutic interventions, follow-up visits, or repeat tracer administrations are planned. Standard-of-care imaging (e.g., FDG-PET/CT, PSMA-PET/CT, CT or MRI) already available for each participant is used as the reference for intra-individual comparison. The total radiation dose is approximately 7 mSv (≈3.5 mSv PET + ≈3.5 mSv low-dose CT), comparable to standard clinical PET/CT exposure. Population: Approximately 770 participants (age ≥18) will be recruited consecutively across 17 indication-specific subgroups: thyroid pathology; head and neck cancer (including cancer of unknown primary); neck node metastases from cancer of unknown primary; sinonasal tract tumor; sarcoidosis; thyroid cancer (suspected recurrence/persistence); breast cancer; hepatocellular carcinoma; gastric cancer; pancreatic cancer; prostate cancer (biochemical recurrence with negative PSMA-PET); urothelial carcinoma; multiple myeloma/plasmocytoma; mesothelioma; hepatic fibrosis; endometriosis; and lung fibrosis. Full eligibility criteria and per-indication enrollment targets are provided in the Eligibility Criteria module. Investigational Medicinal Product: \[18F\]FAPI-74 is a fluorine-18-labelled small-molecule inhibitor targeting FAP. Administered activity is approximately 250 MBq, with a permissible site-specific range of 200-300 MBq. Route of administration is intravenous slow bolus injection (5-15 seconds). The product is manufactured at the USZ Radiopharmacy under GMP conditions, using precursor material supplied by SOFIE Biosciences. Imaging is performed 45-60 minutes post-injection. Procedures: Screening includes eligibility assessment, informed consent, collection of demographic and clinical information, and review of historical imaging. Study Visit (Day 0) includes reconfirmation of eligibility, radiotracer injection, a 45-60 minute uptake phase, PET/CT or PET/MR acquisition, adverse event assessment, and discharge. This is a single-visit study; no follow-up visits are planned. Outcomes: Primary and secondary outcome definitions, including uptake classification, image quality rating, and comparison methodology against reference imaging, are provided in full in the Outcome Measures module. Statistical Methods: The study is descriptive and exploratory in nature. No hypothesis-driven power calculation was performed; sample size was determined based on prior experience with comparable diagnostic imaging studies, published literature, and feasibility considerations. Quality Assurance: Monitoring is performed by the Clinical Trials Center (CTC), University Hospital Zurich, in accordance with ICH-GCP and the Swiss Ordinance on Clinical Trials (ClinO). Study data are collected in REDCap® and pseudonymised; imaging data remain stored in institutional PACS systems under standard institutional access controls. Funding and Insurance: Each participating centre covers its own operational costs. Precursor material for \[18F\]FAPI-74 is supplied by SOFIE Biosciences under contractual agreement. Insurance coverage is provided through the Sponsor-Investigator's institutional policy (Baloise Versicherung AG), in accordance with ClinO Annex 2.