18F-labeled tracers targeting fibroblast activation protein

• Verfasst von: Lindner, Thomas [VerfasserIn]
• Verfasst von: Altmann, Annette [VerfasserIn]
• Verfasst von: Giesel, Frederik L. [VerfasserIn]
• Verfasst von: Kratochwil, Clemens [VerfasserIn]
• Verfasst von: Kleist, Christian [VerfasserIn]
• Verfasst von: Krämer, Susanne [VerfasserIn]
• Verfasst von: Mier, Walter [VerfasserIn]
• Verfasst von: Cardinale, Jens [VerfasserIn]
• Verfasst von: Kauczor, Hans-Ulrich [VerfasserIn]
• Verfasst von: Jäger, Dirk [VerfasserIn]
• Verfasst von: Debus, Jürgen [VerfasserIn]
• Verfasst von: Haberkorn, Uwe [VerfasserIn]
• Titel: 18F-labeled tracers targeting fibroblast activation protein
• Verf.angabe: Thomas Lindner, Annette Altmann, Frederik Giesel, Clemens Kratochwil, Christian Kleist, Susanne Krämer, Walter Mier, Jens Cardinale, Hans-Ulrich Kauczor, Dirk Jäger, Jürgen Debus & Uwe Haberkorn
• E-Jahr: 2021
• Jahr: 21 August 2021
• Umfang: 13 S.
• Fussnoten: Im Titel ist 18 am Anfang hochgestellt ; Gesehen am 17.10.2023
• Titel Quelle: Enthalten in: EJNMMI radiopharmacy and chemistry
• Ort Quelle: [Cham, Switzerland] : Springer International Publishing, 2016
• Jahr Quelle: 2021
• Band/Heft Quelle: 6(2021), Artikel-ID 26, Seite 1-13
• ISSN Quelle: 2365-421X
• DOI: doi:10.1186/s41181-021-00144-x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1865949183
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

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.