Details

Autor(en) / Beteiligte

• Lindner, Thomas
• Altmann, Annette
• Giesel, Frederik
• Kratochwil, Clemens
• Kleist, Christian
• Krämer, Susanne
• Mier, Walter
• Cardinale, Jens
• Kauczor, Hans-Ulrich
• Jäger, Dirk
• Debus, Jürgen
• Haberkorn, Uwe

Titel

18F-labeled tracers targeting fibroblast activation protein

Ist Teil von

• EJNMMI radiopharmacy and chemistry, 2021-08, Vol.6 (1), p.1-13, Article 26

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2021

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• 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 chelator-based 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, radiolabeling 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 performed in HT-1080-FAP xenografted nude mice. [ 18 F]AlF-FAPI-74 was selected for PET/CT imaging in a non-small cell lung cancer (NSCLC) patient. Results In vitro, 18 F-labeled FAPI-derivatives demonstrated high affinity (EC 50  = < 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 18 F-labeled compounds, the NOTA bearing compounds [ 18 F]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 [ 18 F]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, [ 18 F]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 [ 18 F]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 [ 18 F]AlF-based FAP-imaging.