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@ARTICLE{Siegmund:307465,
author = {S. C. Siegmund and E. Novruzov and E. Mamlins and Y. Mori
and S. Otto and M. Canis and T. Watabe and R. P. Baum and R.
A. Werner$^*$ and F. L. Giesel},
title = {{C}urrent status of {FAP} therapy in solid tumors.},
journal = {Seminars in nuclear medicine},
volume = {nn},
issn = {0001-2998},
address = {New York, NY [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2025-03064},
pages = {nn},
year = {2025},
note = {epub},
abstract = {FAP-ligands as novel cancer radiopharmaceuticals in nuclear
medicine have been recently translated successfully into the
clinical space. Particularly small molecules (i.e. FAPI-46,
FAPI-74) and peptides (i.e. FAP-2286, DOTAGA.SA.FAPi) seem
to be some of the most promising molecular probes for
imaging and therapy. Back in 2019, there have been slight
reservations about adopting this new imaging probe, after
the decades of the solidly established role of FDG PET/CT in
oncological imaging. At that time, it was expected that
these novel ligands might challenge Onco-PET as new
cornerstones in the individualized tumor staging and even
beyond. However, FAP-targeted imaging is today not intended
to replace FDG PET/CT, but rather to complement cancer
imaging and therapy, where cancer subtypes exhibit low
glucose metabolism which often leads to moderate or very
insufficient FDG uptake. Recently, numerous FAP-imaging
studies -ranging from single-case reports to larger patient
cohorts and even prospective trials have reinforced the
empirical understanding of FAP-imaging as a potentially
'disruptive' modality compared to FDG PET/CT. The broader
application of FAPI PET/CT has gained momentum, shaping a
new narrative in oncological imaging and beyond. FAPI PET/CT
is now increasingly recognized as a novel imaging agent that
does not aim to replace FDG PET/CT, but rather supports it
by enhancing diagnostic accuracy in specific sub-cohort of
tumor entities, where FDG PET/CT tends to underperform.
Several FAP-derivates- such as FAPI-04, FAPI-46, FAPI-74 for
PET imaging as well as FAPI-34 for SPECT imaging were
rapidly introduced into clinical practice. To date,
FAP-imaging agents have steadily paved their way into
clinical practice, particularly in tumor entities such as
pancreatic ductal adenocarcinoma, gastroesophageal cancers,
and hepatocellular carcinoma. Even in lung cancer, where FDG
PET/CT has long held a well-established and clinically
robust role, FAPI PET/CT has quickly emerged as a strong
competitor, especially in case of lung adenocarcinoma. FAPI
PET/CT has been gaining increasing acceptance beyond
academic and scientific field as a tool for improved
oncological imaging, while FAP theranostics is still in the
elaboration and early translation. In contrast to imaging
probes, FAP-derivates for therapy require a rather long
residence (>48 h) time following successful target-binding
at the cancer-associated fibroblast or FAP-positive tumor
cells to enable the radiotoxic effect (beta- and
alpha-emitter) and deliver enough LET to the cancer
microenvironment. Meanwhile, FAP-based imaging probes are
advancing into the clinical application, with Phase-II/III
clinical trials expected as early as Q4/2025 (NCT07217704
$\&$ NCT07217717). In contrast, FAP-targeted therapeutics
remain in the Phase-I or proof-of-concept stage but brings
hope for patients with systemic disease who are left out and
urgently need additional innovation drives beyond the
standard care. This review article will give insight into
the most recent developments in the FAP-Therapeutic
applications of cancer treatments using several different
promising FAP-derivates to improve FAP-theranostic in
oncology.},
subtyp = {Review Article},
keywords = {(177)Lu (Other) / Cancer-associated fibroblasts (Other) /
FAPI (Other) / Fibroblast activation protein (Other) /
Radioligand therapy (Other) / Solid tumors (Other) /
Theranostics (Other)},
cin = {MU01},
ddc = {610},
cid = {I:(DE-He78)MU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41455672},
doi = {10.1053/j.semnuclmed.2025.11.022},
url = {https://inrepo02.dkfz.de/record/307465},
}