Breast Cancer, Endometriosis (Diagnosis), Gastric Cancer (GC), Head and Neck Cancer (H&N), Hepatic Fibrosis, Hepatocellular Carcinoma (HCC), Lung Fibrosis, Mesothelioma, Multiple Myeloma or Plasmacytoma, Neck Node Metastasis, Pancreatic Cancer, Adult, Prostate Cancer (CRPC), Sarcoidosis, Sinonasal Tract Tumor, Thyroid Cancer, Thyroid Pathology, Urothelial Carcinoma (UC)
Conditions
Keywords
[18F]FAPI-74, Fibroblast Activation Protein, FAP-targeted imaging, PET/CT, Radiotracer, Diagnostic imaging, Multicentric study, Radiopharmaceutical, FAPI, FAPI-74, nuclear medicine, University Hospital Zurich, swiss multicenter trial, Cancer-associated fibroblast imaging, oncologic imaging, non-oncologic imaging
Brief summary
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.
Detailed description
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.
Interventions
18F\]FAPI-74 is a fluorine-18 labelled, quinoline-based small-molecule inhibitor targeting fibroblast activation protein (FAP), a transmembrane glycoprotein selectively expressed on cancer-associated fibroblasts and in fibrotic/inflammatory tissue. Each participant receives a single intravenous slow-bolus injection (5-15 seconds) of approximately 250 MBq (permissible range 200-300 MBq), followed by a 45-60 minute uptake period and one PET/CT or PET/MR acquisition. The product is manufactured under GMP at the USZ Radiopharmacy using precursor material supplied by SOFIE Biosciences. Unlike clinically established PET tracers (e.g., FDG, PSMA-ligands), \[18F\]FAPI-74 is not yet authorized in Switzerland and is administered exclusively within this investigational protocol for diagnostic evaluation purposes only.
Sponsors
Martin Huellner
University Hospital, Zürich
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent obtained and documented by the participant's signature. * Age ≥18 years at the time of consent. * Clinically established or suspected diagnosis or recurrence of an oncologic or non-oncologic disease as defined in chapter 7.1 of study protocol. * Availability of standard-of-care imaging (e.g., clinically established PET tracer or anatomical imaging such as CT/MRI) to allow comparative evaluation.
Exclusion criteria
* Severe claustrophobia that would preclude PET imaging. * Inability to remain still for the duration of the PET/MR examination. * Current pregnancy or breastfeeding; no pregnancy test is required for women who are postmenopausal for ≥12 months or have undergone surgical sterilization, bilateral oophorectomy, or hysterectomy. * Previous hypersensitivity reactions to radiotracer administration * Inability to understand the study information, for example due to language barriers. * Subjects incapable of judgment (e.g. individuals under legal or medical incapacity). * Participants scheduled for PET/MR imaging: Presence of MRI-incompatible metallic implants, electronic devices (e.g. pacemakers, cochlear implants), or other ferromagnetic foreign bodies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Interpretability and Uptake Classification of [18F]FAPI-74 PET Imaging | At the time of [18F]FAPI-74 PET/CT or PET/MR image acquisition and interpretation, performed 45-60 minutes after tracer injection, on the single study visit day. | Qualitative assessment of \[18F\]FAPI-74 uptake by a local nuclear medicine physician, classified as FAPI-positive or FAPI-negative in target lesions or disease-specific regions. Overall diagnostic image quality will additionally be rated using a 4-point scale: fully diagnostic, almost fully diagnostic, diagnostically limited, or non-diagnostic. The primary analysis will report the proportion of participants with diagnostically interpretable \[18F\]FAPI-74 images, per indication and pooled across indications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lesion-Wise Comparison of [18F]FAPI-74 Uptake with Standard-of-Care Reference Imaging | At the time of [18F]FAPI-74 image interpretation, compared against each participant's most recent standard-of-care reference imaging obtained as part of routine clinical care | Qualitative and semi-quantitative comparison of \[18F\]FAPI-74 uptake with each participant's available standard-of-care reference imaging (e.g., FDG-PET/CT, PSMA-PET/CT, or morphological imaging such as CT/MRI), performed on a lesion-wise basis. Comparative ratings will classify \[18F\]FAPI-74 findings as providing more, comparable, or less diagnostic information relative to the reference imaging. Where available, histopathology or composite clinical/imaging follow-up will serve as the reference standard for calculating sensitivity, specificity, and positive predictive value per indication. |
| Change in Diagnostic Confidence and Clinical Management Following [18F]FAPI-74 Imaging | Diagnostic confidence and management recommendations assessed immediately before and after review of [18F]FAPI-74 imaging, on the single study visit day. | Change in diagnostic confidence and clinical management recommendations, determined by comparing physician assessments performed before versus after review of \[18F\]FAPI-74 imaging. Diagnostic confidence will be rated on a defined scale; management change will be recorded as a binary indicator (yes/no), with the type of change categorized (e.g., additional biopsy recommended, therapy switch, change in staging). Clinical impact of \[18F\]FAPI-74 findings will additionally be classified as major impact (change in diagnosis or management), minor impact (additional findings not altering management), or no impact. |
Countries
Switzerland
Contacts
CONTACTMartin Hüllner, Prof. Dr. med.
CONTACTPatrick Perron, Masters Degree
PRINCIPAL_INVESTIGATORMartin Hüllner, Prof. Dr. med.
Department for Nuclear Medicine, University Hospital Zurich
Outcome results
None listed