Fibroblast Activation Protein–Specific PET/CT Imaging in Fibrotic Interstitial Lung Diseases and Lung Cancer: A Translational Exploratory Study

• DOI: 10.2967/jnumed.121.261925
• Publication Date: 2021-07-16T21:10:25Z
• Authors: Manuel Röhrich; Dominik Leitz; Frederik M. Glatting; Annika K. Wefers; Oliver Weinheimer; Paul Flechsig; Nicolas Kahn; Marcus A. Mall; Frederik L. Giesel; Clemens Kratochwil; Peter E. Huber; Andreas von Deimling; Claus Peter Heußel; Hans Ulrich Kauczor; Michael Kreuter; Uwe Haberkorn
• Keywords: Male; Lung Neoplasms; Serine Endopeptidases; Membrane Proteins; Middle Aged; 3. Good health; Translational Research, Biomedical; Mice; 03 medical and health sciences; 0302 clinical medicine; Gelatinases; Positron Emission Tomography Computed Tomography; Endopeptidases; Humans; Animals; Female; Lung Diseases, Interstitial; Aged

Interstitial lung diseases (ILDs) comprise over 200 parenchymal disorders. Among them, fibrosing ILDs, especially idiopathic pulmonary fibrosis, are associated with a poor prognosis, whereas some other such as sarcoidosis, have much better prognosis. A high proportion manifests fibrotic ILD (fILD). Lung cancer (LC) is frequent complication of fILD. Activated fibroblasts crucial for processes in The aim this exploratory study was to evaluate the imaging properties static and dynamic fibroblast activation protein (FAP) inhibitor (FAPI) PET/CT various types fILD confirm FAP expression lesions by immunohistochemistry human biopsy samples sections genetically engineered (<i>Nedd4-2^−/−</i>) mice an fibrosislike disease. <b>Methods:</b> PET scans 15 patients suspected LC were acquired 10, 60, 180 min after administration 150–250 MBq ⁶⁸Ga-labeled FAPI tracer (FAPI-46). In 3 patients, 40 performed instead 10 min. SUV_max SUV_mean measured CT-density–corrected. Target-to-background ratios (TBRs) calculated. correlated CT-based fibrosis scores. Time–activity curves derived from analyzed. 4 lungs <i>Nedd4-2^−/−</i> performed. <b>Results:</b> well showed markedly elevated ⁶⁸Ga-FAPI uptake (density-corrected 60 injection: 11.12 ± 6.71 4.29 1.61, respectively, 16.69 9.35 6.44 3.29, LC) TBR (TBR density-corrected 2.30 1.47 1.67 0.79, 3.90 2.36 2.37 1.14, LC). decreased time, stable trend toward increasing LC. Dynamic differing time–activity positive correlation index. Immunohistochemistry patchy lesions, preferentially transition zone healthy parenchyma. <b>Conclusion:</b>⁶⁸Ga-FAPI promising new modality Its potential clinical value monitoring therapy evaluation should be investigated future studies.