Journal Article

DKFZ-2021-01605

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Fibroblast Activation Protein specific PET/CT imaging in fibrotic interstitial lung diseases and lung cancer: a translational exploratory study.

Röhrich, M. ; Leitz, D. ; Glatting, F. M.DKFZ* ; Wefers, A. K.DKFZ* ; Weinheimer, O. ; Flechsig, P. ; Kahn, N. ; Mall, M. A. ; Giesel, F. L. ; Kratochwil, C. ; Huber, P. E.DKFZ* ; von Deimling, A. ; Heußel, C. P. ; Kauczor, H. U. ; Kreuter, M. ; Haberkorn, U. A.

2022
Soc. New York, NY

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Please use a persistent id in citations: doi:10.2967/jnumed.121.261925

Abstract: Purpose: Interstitial lung diseases (ILD) comprise over 200 parenchymal lung disorders. Among them, fibrosing ILDs, especially idiopathic pulmonary fibrosis (IPF) in particular are associated with a poor prognosis, while some others ILDs like sarcoidosis have a much better prognosis. A high proportion of ILD manifests as fibrotic ILD (fILD). Lung cancer (LC) is a frequent complication of fILD. Activated fibroblasts are crucial for fibrotic processes in fILD. The aim of this exploratory study was to evaluate the imaging properties of static and dynamic FAPI-PET/CT in various types of fILD and to confirm FAP expression of fILD lesions by FAP immunohistochemistry of human fILD biopsy samples and of lung sections of genetically engineered (Nedd4-2 -/- ) mice with an idiopathic pulmonary fibrosis (IPF) -like lung disease. Patients and Methods: PET-Scans of 15 patients with fILD and suspected LC were acquired 10, 60 and 180 minutes after the administration of 150-250 MBq of a 68Ga labelled FAPI tracer (FAPI-46). In three patients, dynamic scans over 40 mins were performed instead of imaging after 10 minutes. Standardized uptake values (SUVmax and SUVmean) of fibrotic lesions and LC were measured and CT-density-corrected. Target-to-background ratios (TBR) were calculated. PET imaging was correlated with CT-based fibrosis scores. Time-activity curves derived from dynamic imaging were analyzed. FAP immunohistochemistry of 4 human fILD biopsy samples and of fibrotic lungs of Nedd4-2-/- mice was carried out. Results: FILD lesions as well as LC showed markedly elevated FAPI-uptake (density corrected SUVmax / mean values 60 minutes post injection: 11,12 +/- 6,71 and 4,29 +/- 1,61 for fILD lesions and 16,69 +/- 9,35 and 6,44 +/- 3,29 for LC) and high TBR (TBR of density corrected SUVmax/SUVmean values 60 minutes post injection: 2,30 +/- 1,47 and 1,67 +/- 0,79 for fILD and 3,90 +/- 2,36 and 2,37 +/- 1,14 for LC). SUVmax and SUVmean values decreased over time with stable TBR of fILD and increasing TBR in LC on trend. Dynamic imaging showed differing time activity curves of fILD and LC. FAPI uptake showed a positive correlation with the CT-based fibrosis index (FIBI). Immunohistochemistry of human biopsy samples and lungs of Nedd4-2-/- mice showed a patchy expression of FAP in fibrotic lesions, preferentially in the transition zone to healthy lung parenchyma. Conclusion: FAPI-PET/CT imaging is a promising new imaging modality for fILD and LC. Its potential clinical value for monitoring and therapy evaluation of fILD should be investigated in future studies.

Keyword(s): Fibroblast Activation Protein ; Interstitial Lung Disease ; Lung Cancer ; PET ; PET/CT ; Respiratory

Note: F E A T U R E D A R T I C L E O F T H E M O N T HFibroblast Activation Protein–Specific PET/CT Imagingin Fibrotic Interstitial Lung Diseases and Lung Cancer:A Translational Exploratory StudyManuel Roehrich1 , Dominik Leitz2 , Frederik M. Glatting3 , Annika K. Wefers4 , Oliver Weinheimer2 , Paul Flechsig1 ,Nicolas Kahn5 , Marcus A. Mall2 , Frederik L. Giesel1 , Clemens Kratochwil1 , Peter E. Huber3 , Andreas von Deimling4 ,Claus Peter Heußel6 , Hans Ulrich Kauczor2 , Michael Kreuter*2 , and Uwe Haberkorn*1 //1 Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany; 2 Translational Lung Research CenterHeidelberg, Member of the German Center for Lung Research DZL, Heidelberg, Germany; 3 Clinical Cooperation Unit Molecular andRadiation Oncology, German Cancer Research Center, Heidelberg, Germany; 4 Department of Neuropathology, Institute of Pathology,University of Heidelberg, Heidelberg, Germany; 5 Centre for Interstitial and Rare Lung Diseases, Pneumology and Respiratory CriticalCare Medicine, Thorax Clinic, University of Heidelberg, Heidelberg, Germany; and 6 Diagnostic and Interventional Radiology withNuclear Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany

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Contributing Institute(s):

1. E055 KKE Molekulare Radioonkologie (E055)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2021

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; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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