Correlation of FAPI PET Uptake with Immunohistochemistry in Explanted Lungs from Patients with Advanced Interstitial Lung Disease.

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  • Additional Information
    • Source:
      Publisher: Society of Nuclear Medicine Country of Publication: United States NLM ID: 0217410 Publication Model: Electronic Cited Medium: Internet ISSN: 1535-5667 (Electronic) Linking ISSN: 01615505 NLM ISO Abbreviation: J Nucl Med Subsets: MEDLINE
    • Publication Information:
      Publication: Reston, VA : Society of Nuclear Medicine
      Original Publication: [Chicago, Ill.] : S.N. Turiel & Assoc.
    • Subject Terms:
      Lung Diseases, Interstitial*/diagnostic imaging ; Lung Diseases, Interstitial*/metabolism ; Immunohistochemistry* ; Lung*/diagnostic imaging ; Lung*/metabolism ; Positron-Emission Tomography*; Humans ; Male ; Female ; Middle Aged ; Aged ; Biological Transport ; Lung Transplantation ; Membrane Proteins ; Endopeptidases ; Quinolines
    • Abstract:
      Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of 68 Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis ( n = 2), rheumatoid arthritis-associated ILD ( n = 1), and nonspecific interstitial pneumonia ( n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUV max and SUV mean showed a positive correlation with the immunohistochemical FAP expression score (SUV max : r = 0.57, P = 0.001; SUV mean : r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.
      (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)
    • Grant Information:
      K23 HL150237 United States HL NHLBI NIH HHS
    • Contributed Indexing:
      Keywords: FAPI; PET; immunohistochemistry; interstitial lung diseases; lung transplantation
    • Accession Number:
      0 (68Ga-FAPI)
      EC 3.4.21.- (fibroblast activation protein alpha)
      0 (Membrane Proteins)
      EC 3.4.- (Endopeptidases)
      0 (Quinolines)
    • Publication Date:
      Date Created: 20241003 Date Completed: 20241101 Latest Revision: 20241106
    • Publication Date:
      20241106
    • Accession Number:
      10.2967/jnumed.124.268351
    • Accession Number:
      39362770