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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 6/2022

Open Access 01-05-2022 | Breast Cancer | Original Article

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

Authors: P. Backhaus, F. Gierse, M. C. Burg, F. Büther, I. Asmus, P. Dorten, J. Cufe, W. Roll, D. Neri, S. Cazzamalli, J. Millul, J. Mock, A. Galbiati, A. Zana, K. P. Schäfers, S. Hermann, M. Weckesser, J. Tio, S. Wagner, H.-J. Breyholz, M. Schäfers

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2022

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Abstract

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 [68Ga]Ga-OncoFAP-DOTAGA (68Ga-OncoFAP) radiolabeling, benchmark its properties in preclinical imaging, and evaluate its application in clinical PET scanning.

Methods

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.

Results

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).

Conclusion

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.
Appendix
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Metadata
Title
Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA
Authors
P. Backhaus
F. Gierse
M. C. Burg
F. Büther
I. Asmus
P. Dorten
J. Cufe
W. Roll
D. Neri
S. Cazzamalli
J. Millul
J. Mock
A. Galbiati
A. Zana
K. P. Schäfers
S. Hermann
M. Weckesser
J. Tio
S. Wagner
H.-J. Breyholz
M. Schäfers
Publication date
01-05-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-021-05653-0

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