Translational imaging of the fibroblast activation protein (FAP) using the new ligand [ 68 Ga]Ga-OncoFAP-DOTAGA.

Autor: Backhaus P; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany. Philipp.backhaus@ukmuenster.de.; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, 48149, Münster, Germany. Philipp.backhaus@ukmuenster.de., Gierse F; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, 48149, Münster, Germany., Burg MC; Clinic for Radiology, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany., Büther F; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany.; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, 48149, Münster, Germany., Asmus I; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany., Dorten P; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, 48149, Münster, Germany., Cufe J; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany.; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, 48149, Münster, Germany., Roll W; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany., Neri D; Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 4, CH-8093, Zurich, Switzerland.; Philogen SpA, Piazza La Lizza 7, 53100, Siena, Italy., Cazzamalli S; Philochem AG, Libernstrasse 3, CH-8112, Otelfingen, Switzerland., Millul J; Philochem AG, Libernstrasse 3, CH-8112, Otelfingen, Switzerland., Mock J; Philochem AG, Libernstrasse 3, CH-8112, Otelfingen, Switzerland., Galbiati A; Philochem AG, Libernstrasse 3, CH-8112, Otelfingen, Switzerland., Zana A; Philochem AG, Libernstrasse 3, CH-8112, Otelfingen, Switzerland., Schäfers KP; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, 48149, Münster, Germany., Hermann S; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, 48149, Münster, Germany., Weckesser M; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany., Tio J; Department of Gynecology & Obstetrics, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany., Wagner S; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany., Breyholz HJ; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany., Schäfers M; Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer Campus 1, Building A1, 48149, Münster, Germany.; European Institute for Molecular Imaging, University of Münster, Waldeyerstraße 15, 48149, Münster, Germany.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2022 May; Vol. 49 (6), pp. 1822-1832. Date of Electronic Publication: 2021 Dec 27.
DOI: 10.1007/s00259-021-05653-0
Abstrakt: Purpose: The fibroblast activation protein (FAP) is an emerging target for molecular imaging and therapy in cancer. OncoFAP is a novel small organic ligand for FAP with very high affinity. In this translational study, we establish [ 68 Ga]Ga-OncoFAP-DOTAGA ( 68 Ga-OncoFAP) radiolabeling, benchmark its properties in preclinical imaging, and evaluate its application in clinical PET scanning.
Methods: 68 Ga-OncoFAP was synthesized in a cassette-based fully automated labeling module. Lipophilicity, affinity, and serum stability of 68 Ga-OncoFAP were assessed by determining logD 7.4 , IC 50 values, and radiochemical purity. 68 Ga-OncoFAP tumor uptake and imaging properties were assessed in preclinical dynamic PET/MRI in murine subcutaneous tumor models. Finally, biodistribution and uptake in a variety of tumor types were analyzed in 12 patients based on individual clinical indications that received 163 ± 50 MBq 68 Ga-OncoFAP combined with PET/CT and PET/MRI.
Results: 68 Ga-OncoFAP radiosynthesis was accomplished with high radiochemical yields. Affinity for FAP, lipophilicity, and stability of 68 Ga-OncoFAP measured are ideally suited for PET imaging. PET and gamma counting-based biodistribution demonstrated beneficial tracer kinetics and high uptake in murine FAP-expressing tumor models with high tumor-to-blood ratios of 8.6 ± 5.1 at 1 h and 38.1 ± 33.1 at 3 h p.i. Clinical 68 Ga-OncoFAP-PET/CT and PET/MRI demonstrated favorable biodistribution and kinetics with high and reliable uptake in primary cancers (SUV max 12.3 ± 2.3), lymph nodes (SUV max 9.7 ± 8.3), and distant metastases (SUV max up to 20.0).
Conclusion: Favorable radiochemical properties, rapid clearance from organs and soft tissues, and intense tumor uptake validate 68 Ga-OncoFAP as a powerful alternative to currently available FAP tracers.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje