The Investigators Will Evaluate the Diagnostic Performance of [18F]-AlF-FAPI-74 PET/CT in Inflammatory Disorders and Compare it With the Current Gold Standard for Inflammation, FDG PET/CT, in Three Patient Cohort: Patients Presenting With Fever of Unknown Origin, IgG4-RD and AxSpA.

Prospective Diagnostic Performance of PET/CT Using the Novel Fibroblast Imaging Tracer [18F]-AlF-FAPI-74 Versus Standard of Care [18F]-FDG in Inflammatory Disorders

The aim of the study to evaluate the performance of new [18F]-AlF-FAPI-74 PET/CT in three inflammatory disorders (fever of unknown origin, IgG4-related disease and axial spondyloarthritis) and compare with the current stand-of-care [18F]-FDG PET/CT

Study Overview

• Status: Recruiting
• Conditions: Fever of Unknown Origin; IgG4 Related Disease; Axial Spondylarthritis (axSpA); Inflammation of Unknown Origin
• Intervention / Treatment: Diagnostic test: [18F]AlF-FAPI-74 PET/CT

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Lennert Boeckxstaens, MD; Phone Number: +0032 16 34 37 15; Email: lennert.boeckxstaens@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospital Leuven
    • Contact: Lennert Boeckxstaens, MD; Phone Number: 0032 1634 37 15; Email: lennert.boeckxstaens@uzleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria FUO:

• An illness of more than 3 weeks' duration,
• Temperature exceeding 38.3°C on > 3 occasions, or elevated inflammatory markers on > 3 occasions
• Diagnosis uncertain despite appropriate first-line investigations.

Inclusion criteria IgG4-RD:

• High clinical suspicion of IgG4-RD by an experienced clinician of Internal Medicine, based on anamnesis, physical examination, first-line investigations and blood tests.
• Patients with a new diagnosis of IgG4-RD on histopathology and need for further assessment of disease extent with PET/CT,
• Relapse of diagnosed IgG4-RD on histopathology according to an experienced clinician of Internal Medicine

Inclusion criteria AxSpA:

• High clinical suspicion of axial spondyloarthropahy according to an experienced rheumatology (based on inflammary back pain > 3 months, insidious onset, morning stifness, improvement with exercise and worsening in rest, pain worse at night, age at onset <45 years of age, imaging findings).
• Patient has persisting inflammatory back pain after 2 different types of NSAID's (tried for over 2-4 weeks), and is therefore eligible for biological DMARDS therapy.

Exclusion Criteria:

• Participant is mentally or legally incapacitated, doesn't understand the study design or is not willing or capable to undergo all study-specific procedures.
• Any disorder or condition, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol.
• Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.
• Female who is pregnant (urinary hCG test will be performed in every WOCBP), breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive (with a relatively high Pearl Index: natural methods, minipill outside postpartum period, spermicides or condoms in monotherapy or no usage of contraception when sexually active are not accepted).
• Participation in an interventional Trial with an investigational medicinal product (IMP) or device when the trial designs are not considered compatible by the study team.
• Participation in a clinical scientific study in the last 12 months with a radiation exposure caused by the experimental procedures greater than 1 mSv.
• Participant has a known hypersensitivity to [18F]AlF-FAPI-74 or the used excipients.
• Active treatment has already commenced

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Axial Spondyloarthritis	Diagnostic test: [18F]AlF-FAPI-74 PET/CT; A [18F]AlF-FAPI-74 PET/CT will be performed at the same site of the screening visit (UZ Leuven). The patient will get an IV line, through which the [18F]AlF-FAPI-74 will be injected in one bolus (3,5 MBq/kg). After 60 minutes, the acquisition on the PET/CT scan will take place. The CT will be a low dose CT with oral contrast. After the scan, participants will be observed at the department in case of adverse events. If the patient receives therapy (for IgG4-RD and AxSpA), a second [18F]AlF-FAPI-74 PET/CT will be performed three months later.
Experimental: FUO/IUO	Diagnostic test: [18F]AlF-FAPI-74 PET/CT; A [18F]AlF-FAPI-74 PET/CT will be performed at the same site of the screening visit (UZ Leuven). The patient will get an IV line, through which the [18F]AlF-FAPI-74 will be injected in one bolus (3,5 MBq/kg). After 60 minutes, the acquisition on the PET/CT scan will take place. The CT will be a low dose CT with oral contrast. After the scan, participants will be observed at the department in case of adverse events. If the patient receives therapy (for IgG4-RD and AxSpA), a second [18F]AlF-FAPI-74 PET/CT will be performed three months later.
Experimental: IgG4-related disease	Diagnostic test: [18F]AlF-FAPI-74 PET/CT; A [18F]AlF-FAPI-74 PET/CT will be performed at the same site of the screening visit (UZ Leuven). The patient will get an IV line, through which the [18F]AlF-FAPI-74 will be injected in one bolus (3,5 MBq/kg). After 60 minutes, the acquisition on the PET/CT scan will take place. The CT will be a low dose CT with oral contrast. After the scan, participants will be observed at the department in case of adverse events. If the patient receives therapy (for IgG4-RD and AxSpA), a second [18F]AlF-FAPI-74 PET/CT will be performed three months later.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
FUO/IUO: Demonstrate that the diagnostic performance of [18F]AlF-FAPI-74 PET/CT is equivalent or superior to the current gold standard, [18F] FDG PET/CT, in contributing to the final diagnosis (non-inferiority study with non-inferiority limit (10%)	6 months after completion of both PET/CT scans
IgG4-RD: Demonstrate that the diagnostic performance of [18F]AlF-FAPI-74 PET/CT is superior to [18F]FDG PET/CT, in patients with suspicion of IgG4-RD and assessment of disease extent in patients with confirmed or relapsed IgG4-RD.	After completion of both PET/CT scans before initiation of treatment and after completion of both PET/CT scans 3 months completion of treatment.
Axial Spondyloarthritis: evaluate the diagnostic accuracy of [18F]AlF-FAPI-74 PET/CT in differentiating inflammatory back pain in patients with axSpA from patients with mechanical back pain, and evaluate the ability to assess treatment response	After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
FUO/IUO: Determine the distribution of the four major causal group in FUO/IUO (infectious, inflammatory, malignant, and miscellaneous) of both tracers and evaluate for which causal groups [18F]AlF-FAPI-74 PET/CT is superior to [18F]FDG PET/CT.	6 months after completion of all PET/CT scans
FUO/IUO: Evaluate for which entities [18F]AlF-FAPI-74 has the potential to outperform [18F]FDG PET/CT in lager patient cohorts.	6 months after completion of all PET/CT scans
FUO/IUO: Determine the ratio of true positives, true negatives, false positives, false negative, positive predictive value, and negative predictive value.	6 months after completion of all PET/CT scans
IgG4-RD: Semi-quantitative uptake measurements (maximal standardized uptake value (SUVmax), average SUV (SUVmean), peak SUV (SUVpeak) of lesions on [18F]AlF-FAPI-74 PET/CT and [18F]FDG PET/CT.	After completion of both PET/CT scans before initiation of treatment and after completion of both PET/CT scans 3 months completion of treatment.
IgG4-RD: Evaluate the organ detection ratio for every organ, defined as the percentage of patients with pathological uptake in that specific organ by each tracer for the total of number of patients with pathological uptake in that organ	After completion of both PET/CT scans before initiation of treatment and after completion of both PET/CT scans 3 months completion of treatment.
IgG4-RD: 4) Evaluate the total number of affected organs per patient for each tracer and calculate the difference for both tracers. Determine the total difference of affected organs between both tracers for all patients.	After completion of both PET/CT scans before initiation of treatment and after completion of both PET/CT scans 3 months completion of treatment.
IgG4-RD: Evaluate the treatment response of FAPI and FDG lesions by quantifying the change in SUVmax between baseline and post-therapy PET/CT scans.	After completion of both PET/CT scans before initiation of treatment and after completion of both PET/CT scans 3 months completion of treatment.
AxSpA: Semi-quantitative uptake measurements (maximal standardized uptake value (SUVmax), target-to-background (TBR)) of lesions in the spine and the sacro-iliac joints will be computed on [18F]AlF-FAPI-74 PET/CT in all patients	After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment
AxSpA: Determine if there is a significant statistical difference (p<0.05) in semi-quantitative uptake measurements (SUVmax, TBR) between the two cohorts, and determine the optimal cut-off value.	After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment
AxSPa: Assess treatment response by evaluating changes in semi-quantitative measurements (SUVmax, TBR) in patients with axSpA following 3 month treatment with bDMARDs.	After completion of first PET/CT scan and after completion of PET/CT scan performed 3 months after treatment

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2025
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 17, 2026

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Body Temperature Changes; Fever; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Immunoglobulin G4-Related Disease; Fever of Unknown Origin
• Other Study ID Numbers: S69207 - 2024-516464-28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No