Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA. [Translationale Bildgebung des Fibroblastenaktivierungsproteins (FAP) unter Verwendung des neuen Liganden [68Ga]Ga-OncoFAP-DOTAGA]

Backhaus P; Gierse F; Burg MC; Büther F; Asmus I; Dorten P; Cufe J; Roll W; Neri D; Cazzamalli S; Millul J; Mock J; Galbiati A; Zana A; Schäfers KP; Hermann S; Weckesser M; Tio J; Wagner S; Breyholz HJ; Schäfers M

Research article (journal) | Peer reviewed

Abstract

PURPOSE - METHODS - RESULTS - CONCLUSION; 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 [68Ga]Ga-OncoFAP-DOTAGA (68Ga-OncoFAP) radiolabeling, benchmark its properties in preclinical imaging, and evaluate its application in clinical PET scanning.; 68Ga-OncoFAP was synthesized in a cassette-based fully automated labeling module. Lipophilicity, affinity, and serum stability of 68Ga-OncoFAP were assessed by determining logD7.4, IC50 values, and radiochemical purity. 68Ga-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 68Ga-OncoFAP combined with PET/CT and PET/MRI.; 68Ga-OncoFAP radiosynthesis was accomplished with high radiochemical yields. Affinity for FAP, lipophilicity, and stability of 68Ga-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 68Ga-OncoFAP-PET/CT and PET/MRI demonstrated favorable biodistribution and kinetics with high and reliable uptake in primary cancers (SUVmax 12.3 ± 2.3), lymph nodes (SUVmax 9.7 ± 8.3), and distant metastases (SUVmax up to 20.0).; Favorable radiochemical properties, rapid clearance from organs and soft tissues, and intense tumor uptake validate 68Ga-OncoFAP as a powerful alternative to currently available FAP tracers.

Details about the publication

JournalEuropean Journal of Nuclear Medicine and Molecular Imaging (Eur J Nucl Med Mol Imaging)
Volume49
Issue6
Page range1822-1832
StatusPublished
Release year2022 (31/05/2022)
Language in which the publication is writtenEnglish
DOI10.1007/s00259-021-05653-0
Link to the full texthttps://pmc.ncbi.nlm.nih.gov/articles/PMC9016025/
KeywordsAnimals; Fibroblasts; Gallium Radioisotopes; Humans; Ligands; Mice; Neoplasms; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Tissue Distribution

Authors from the University of Münster

Asmus, Inga
Clinic for Nuclear Medicine
Backhaus, Philipp
Clinic for Nuclear Medicine
Breyholz, Hans-Jörg
Clinic for Nuclear Medicine
Burg, Matthias
Clinic of Radiology
Cufe, Juela
Clinic for Nuclear Medicine
Dorten, Paulina Marie
European Institute of Molecular Imaging (EIMI)
Gierse, Florian Werner
University Children's Hospital - Department of Paediatric Haematology and Oncology (UKM PHO)
Hermann, Sven
European Institute of Molecular Imaging (EIMI)
Roll, Wolfgang
Clinic for Nuclear Medicine
Schäfers, Michael
Clinic for Nuclear Medicine
Wagner, Stefan
Clinic for Nuclear Medicine
Weckesser, Jochen Matthias
Clinic for Nuclear Medicine