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DETECTION OF FIBROSIS AND DIFFERENTIATION FROM INFLAMMATION IN IBD PATIENTS USING FAPI PET/CT IMAGING: THE PIMAFI STUDY

Dalia Alexia Lartey 1, Kelly van Wijnbergen 1, Bo Jun Ke 2, Christianne Johanna Buskens 1, Jarmila van Der Bilt 3, Gianluca Matteoli 2, Gert De Hertogh 4, Joep Grootjans 1, Manon E. Wildenberg 5, Sanne E. Wiegers 1, Maqsood M. Yaqub 1, Geert R. D'Haens 1, Gerben J. C. Zwezerijnen 1, Mark Löwenberg 1

Affiliations

1 Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands

2 KU Leuven, Leuven, Belgium

3 Flevoziekenhuis, Almere, Netherlands

4 University Hospital Leuven, Leuven, Belgium

5 AMC Amsterdam, Amsterdam, Netherlands

Summary

AI Generated

First in-human study demonstrates that 68Ga-FAPi PET/CT imaging can detect and quantify intestinal fibrosis in inflammatory bowel disease patients, with uptake patterns correlating with histological fibrosis and FAP expression in surgical specimens.

In 19 IBD patients (15 Crohn's disease, 4 ulcerative colitis) awaiting surgery, 68Ga-FAPi PET/CT tracer uptake was markedly increased in inflamed and fibrotic bowel regions compared to reference segments, with SUV50-60 values ranging 1.0 to 11 versus 0.3 to 1.1
Pharmacokinetic analysis of time-activity curves distinguished fibrotic from inflammatory segments: inflammatory regions showed high peak uptake followed by decline (suggesting reversible, potentially non-specific uptake), while fibrotic segments showed low peak followed by stable plateau (suggesting irreversible, higher binding affinity uptake)
Tracer uptake aligned with histological fibrosis scoring and enhanced FAP gene and protein expression in 52 transmural surgical samples, supporting the potential of 68Ga-FAPi PET/CT to differentiate fibrosis from inflammation non-invasively
This imaging approach addresses an unmet need in IBD, as reliable intestinal fibrosis imaging modalities are currently lacking and hamper anti-fibrotic therapy development

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This summary was generated by an AI large language model based on the content transcript. It is for informational purposes only and should not be considered a substitute for clinical judgment. Always rely on your professional expertise and the full clinical context when making clinical decisions.

Abstract

Introduction

The lack of reliable intestinal fibrosis imaging modalities hampers anti-fibrotic therapy development. Gallium-68 Fibroblast Activation Protein inhibitor (⁶⁸GaFAPi) PET/CT offers promising in vivo fibrosis visualization via Fibroblast Activation Protein (FAP) targeting. Despite reported overexpression of FAP in chronic inflammatory and fibrotic diseases, data in inflammatory bowel disease (IBD) and the potential use of ⁶⁸Ga-FAPi PET/CT as a non-invasive fibrosis biomarker remains sparse. We performed the first in-human study to investigate ⁶⁸Ga-FAPi PET/CT to detect and quantify fibrosis in IBD patients using pharmacokinetic modelling.

Aims & Methods

Symptomatic patients with active Crohn’s disease (CD) or ulcerative colitis (UC) waiting for surgical resection were invited to the study and consented. Patients underwent a 60-minute dynamic ⁶⁸Ga-FAPi PET/CT scan, followed by 12 minutes of static imaging within 12 weeks before surgery. Arterial and peripheral blood samples were obtained during the first 10 scans to validate image- versus plasma-derived input function. Two blinded readers independently assessed the PET/CT images, wherein bowel segments showing increased uptake against local background were delineated and validated by a non-blinded third reader. Bowel segment uptake, time-activity-curves (TAC) and input functions were analyzed using irreversible (2T3k), reversible two-tissue compartment models (2T4k), reference tissue models, and standardized uptake values acquired on static images 50-60 minutes post-injection (SUV_50-60). Surgical resection specimens were selected based on ⁶⁸Ga-FAPi PET/CT with focus on segments with high FAPi uptake. In the tissue samples, gene expression and protein levels of FAP were determined using quantitative polymerase chain reaction (qPCR) and immunohistochemistry. To allocate samples to a fibrotic, inflamed or combined phenotype, hematoxylin and eosin and Masson’s trichrome staining were performed for inflammatory activity and fibrosis scoring by a blinded pathologist (GH) using previously described histological inflammation and fibrosis scores.¹

Results

In total, 15 CD and 4 UC patients (mean age 39 years, median disease duration 12 years) underwent FAPi PET/CT prior to surgery. On these 19 scans, 50 bowel regions of interest were identified and 52 transmural surgical samples were acquired. FAPi tracer uptake was markedly increased in inflamed and fibrotic regions of all participants compared to reference, non-pathologic bowel segments (SUV_50-60ranging 1.0 to 11 versus 0.3 to 1.1). Although a higher tracer activity was seen in all patients, the inflammatory bowel segments showed the highest peak in tracer activity, followed by a decline in uptake, indicating increased blood flow, vascular permeability and reversible, potentially non-specific or low-binding affinity, uptake. Contrarily, the TAC of patients with a more fibrotic phenotype, showed a low peak uptake followed by a relatively stable plateau, suggesting a more irreversible or higher binding affinity uptake component.

Conclusion

⁶⁸Ga-FAPi PET/CT shows significant promise for IBD assessment as uptake aligns with histological fibrosis scoring, enhanced FAP gene and protein expression in resected inflammatory and stenotic specimens in CD and UC patients. Pharmacokinetic analyses suggests more frequent irreversible uptake kinetics, indicating higher FAP binding affinity, in predominantly fibrotic segments compared to inflamed regions, thus underscoring its potential to differentiate fibrosis from inflammation.

References

1. Ke BJ, Abdurahiman S, Biscu F, Zanella G, et al. Intercellular interaction between FAP+ fibroblasts and CD150+ inflammatory monocytes mediates fibrostenosis in Crohn's disease. J Clin Invest. 2024 Jul 23;134(16):e173835. doi: 10.1172/JCI173835. PMID: 39042469; PMCID: PMC11324301.

Disclosure

M.L.: Consultancy/lecture fees from Abbvie, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda, Tillotts. Central reader for Alimentiv. Grants received from ZonMW, Galapagos, NFU transformation deal, and TKI (unrelated)
G.R.A.M.D.: research grants from Abbvie, Alimentiv, BMS, J&J, Pfizer, Takeda; consulting fees from Abbvie, Agomab, Alimentiv, AstraZeneca, AMT, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Index Pharmaceuticals, Glaxo Smith Kline, Pfizer, Johnson and Johnson, Polpharma, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, Protagonist, and Ventyx; speaker’s fees from Abbvie, Celltrion, Galapagos, Pfizer, and Takeda; data monitoring board: Galapagos, AstraZeneca, Seres Health (unrelated)

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Advances in fibrosis research in Crohn's disease (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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