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Lindner, Thomas [Author]; Altmann, Annette [Author]; Giesel, Frederik L. [Author]; Kratochwil, Clemens [Author]; Kleist, Christian [Author]; Krämer, Susanne [Author]; Mier, Walter [Author]; Cardinale, Jens [Author]; Kauczor, Hans-Ulrich [Author]; Jäger, Dirk [Author]; Debus, Jürgen [Author]; Haberkorn, Uwe [Author]

18F-labeled tracers targeting fibroblast activation protein

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  • Media type: E-Article
  • Title: 18F-labeled tracers targeting fibroblast activation protein
  • Contributor: Lindner, Thomas [VerfasserIn]; Altmann, Annette [VerfasserIn]; Giesel, Frederik L. [VerfasserIn]; Kratochwil, Clemens [VerfasserIn]; Kleist, Christian [VerfasserIn]; Krämer, Susanne [VerfasserIn]; Mier, Walter [VerfasserIn]; Cardinale, Jens [VerfasserIn]; Kauczor, Hans-Ulrich [VerfasserIn]; Jäger, Dirk [VerfasserIn]; Debus, Jürgen [VerfasserIn]; Haberkorn, Uwe [VerfasserIn]
  • imprint: 21 August 2021
  • Published in: EJNMMI radiopharmacy and chemistry ; 6(2021), 1, Seite 1-13
  • Language: English
  • DOI: 10.1186/s41181-021-00144-x
  • ISSN: 2365-421X
  • Identifier:
  • Origination:
  • Footnote: Im Titel ist 18 am Anfang hochgestellt
  • Description: Background:  Cancer-associated fibroblasts are found in the stroma of epithelial tumors. They are characterized by overexpression of the fibroblast activation protein (FAP), a serine protease which was already proven as attractive target for chelatorbased theranostics. Unfortunately, the value of gallium-68 labeled tracers is limited by their batch size and the short nuclide half-life. To overcome this drawback, radiolabe‑ling with aluminum fluoride complexes and 6-fluoronicotinamide derivatives of the longer-lived nuclide fluorine-18 was established. The novel compounds were tested for their FAP-specific binding affinity. Uptake and binding competition were studied in vitro using FAP expressing HT-1080 cells. HEK cells transfected with the closely related dipeptidyl peptidase-4 (HEK-CD26) were used as negative control. Small animal positron emission tomography imaging and biodistribution experiments were per‑formed in HT-1080-FAP xenografted nude mice. ­[18F]AlF-FAPI-74 was selected for PET/ CT imaging in a non-small cell lung cancer (NSCLC) patient. - Results:  In vitro, 18F-labeled FAPI-derivatives demonstrated high affinity (­EC50 = < 1 nm to 4.2 nm) and binding of up to 80% to the FAP-expressing HT1080 cells while no binding to HEK-CD26 cells was observed. While small animal PET imaging revealed unfavorable biliary excretion of most of the 18F-labeled compounds, the NOTA bearing compounds ­[18F]AlF-FAPI-74 and -75 achieved good tumor-to-background ratios, as a result of their preferred renal excretion. These two compounds showed the highest tumor accumulation in PET imaging. The organ distribution values of ­[18F]AlF-FAPI-74 were in accordance with the small animal PET imaging results. Due to its less complex synthesis, fast clearance and low background values, ­[18F]AlF-FAPI-74 was chosen for clinical imaging. PET/CT of a patient with metastasized non-small cell lung cancer (NSCLC), enabled visualization of the primary tumor and its metastases at the hepatic portal and in several bones. This was accompanied by a rapid clearance from the blood pool and low background in healthy organs. - Conclusion: [18F]AlF-labeled FAPI derivatives represent powerful tracers for PET. Owing to an excellent performance in PET imaging, FAPI-74 can be regarded as a promising precursor for ­[18F]AlF-based FAP-imaging.
  • Access State: Open Access