In:
European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 49, No. 6 ( 2022-05), p. 1822-1832
Abstract:
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 log D 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.
Type of Medium:
Online Resource
ISSN:
1619-7070
,
1619-7089
DOI:
10.1007/s00259-021-05653-0
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2098375-X
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