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@ARTICLE{Hosseini:304505,
author = {A. Hosseini and E. Haj-Yehia and S. Korste and Y. Kuzay and
M. Trajkovic-Arsic$^*$ and S. Settelmeier and M. Cantore and
K. B. Ferenz and J. T. Siveke$^*$ and K. Herrmann and T.
Rassaf and U. Hendgen-Cotta and W. A. Weber and Z. Varasteh},
title = {{H}ow {R}apidly {D}oes the {FAPI} {PET} {S}ignal {R}everse
{F}ollowing {T}herapy? {A}ssessing the {FAPI} {PET} {S}ignal
in {H}ypertensive {C}ardiac {I}njury and {F}ibrosis in
{M}ice.},
journal = {Journal of nuclear medicine},
volume = {nn},
issn = {0097-9058},
address = {New York, NY},
publisher = {Soc.},
reportid = {DKFZ-2025-01893},
pages = {nn},
year = {2025},
note = {epub},
abstract = {Reactive fibrosis is a complex response to chronic
myocardial insults, contributing to heart failure
progression. Fibroblast activation protein inhibitor (FAPI)
PET shows promise in distinguishing active from established
fibrosis. Although antifibrotic therapies may improve left
ventricular (LV) function in preclinical studies, their
clinical application is limited by the lack of noninvasive
imaging methods to assess fibrosis regression. This study
investigates the potential of FAPI PET to track the
therapeutic transition of activated fibroblast activation
protein (FAP)-positive fibroblasts toward a FAP-negative
phenotype. Methods: Mice were implanted with minipumps,
infused with angiotensin-II/phenylephrine (Ang-II/PE) for 6
wk and scanned with 68Ga-FAPI-46 PET/CT longitudinally.
Control mice received saline. 68Ga-FAPI-46 biodistribution
studies were conducted at preselected time points, and FAPI
uptake in the major organs was measured ex vivo. To assess
the potential reversibility of the FAPI PET signal in the
myocardium and liver, Ang-II/PE infusion was discontinued in
a group of animals at 1 and 2 wk, respectively. LV
structural and functional changes were assessed via
echocardiography, tissue fibrosis via histology, and FAP
expression via immunohistochemistry. Results: Significant
68Ga-FAPI-46 uptake in the myocardium of treated mice peaked
at 1 wk. An increase of 68Ga-FAPI-46 uptake was also
observed in the liver, peaking at 2 wk, and decreased
significantly at 4 wk. The PET signal declined to an
indiscernible level in the heart and liver early after
Ang-II/PE withdrawal. Three weeks after the removal of the
minipumps, the hearts of mice previously exposed to
Ang-II/PE for 1 wk exhibited a significant reduction in
fibrosis compared with mice that were sacrificed immediately
after 1 wk of Ang-II/PE infusion, without the 3-wk recovery
period. Coinjection with excess unlabeled FAPI-46 reduced
uptake in the heart, liver, and kidneys. Despite an increase
in LV wall thickness at 1 wk, the ejection fraction remained
stable initially but dropped significantly by 4 wk.
Conclusion: The rapid decline in PET signal after Ang-II/PE
withdrawal shows that FAPI PET effectively visualizes
dynamic changes in FAP expression, making it a valuable tool
for quickly assessing treatment responses targeting
activated fibroblasts. The cardiac FAPI signal precedes
functional myocardial changes, indicating that FAPI PET
could detect early fibrosis in cardiac remodeling leading to
heart failure. FAPI PET may also visualize cardiac
cirrhosis, a serious complication of cardiac disorders.},
keywords = {FAPI PET (Other) / rapid therapy response monitoring
(Other) / signal reversibility (Other)},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40935615},
doi = {10.2967/jnumed.124.268860},
url = {https://inrepo02.dkfz.de/record/304505},
}