RT Journal Article
SR Electronic
T1 Fibroblast Activation Protein specific PET/CT imaging in fibrotic interstitial lung diseases and lung cancer: a translational exploratory study.
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.121.261925
DO 10.2967/jnumed.121.261925
A1 Manuel Röhrich
A1 Dominik Leitz
A1 Frederik M. Glatting
A1 Annika K. Wefers
A1 Oliver Weinheimer
A1 Paul Flechsig
A1 Nicolas Kahn
A1 Markus A. Mall
A1 Frederik L. Giesel
A1 Clemens Kratochwil
A1 Peter E. Huber
A1 Andreas von Deimling
A1 Claus Peter Heußel
A1 Hans Ulrich Kauczor
A1 Michael Kreuter
A1 Uwe A. Haberkorn
YR 2021
UL http://jnm.snmjournals.org/content/early/2021/07/16/jnumed.121.261925.abstract
AB 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.