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@ARTICLE{Rhrich:169871,
      author       = {M. Röhrich and D. Leitz and F. M. Glatting$^*$ and A. K.
                      Wefers$^*$ and O. Weinheimer and P. Flechsig and N. Kahn and
                      M. A. Mall and F. L. Giesel and C. Kratochwil and P. E.
                      Huber$^*$ and A. von Deimling and C. P. Heußel and H. U.
                      Kauczor and M. Kreuter and U. A. Haberkorn},
      title        = {{F}ibroblast {A}ctivation {P}rotein specific {PET}/{CT}
                      imaging in fibrotic interstitial lung diseases and lung
                      cancer: a translational exploratory study.},
      journal      = {Journal of nuclear medicine},
      volume       = {63},
      number       = {1},
      issn         = {2159-662X},
      address      = {New York, NY},
      publisher    = {Soc.},
      reportid     = {DKFZ-2021-01605},
      pages        = {127-133},
      year         = {2022},
      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},
      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.},
      keywords     = {Fibroblast Activation Protein (Other) / Interstitial Lung
                      Disease (Other) / Lung Cancer (Other) / PET (Other) / PET/CT
                      (Other) / Respiratory (Other)},
      cin          = {E055},
      ddc          = {610},
      cid          = {I:(DE-He78)E055-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34272325},
      doi          = {10.2967/jnumed.121.261925},
      url          = {https://inrepo02.dkfz.de/record/169871},
}