Heart failure has become a leading cause of morbidity, mortality, and economic burden worldwide. The cause of heart failure include aging, diabetes, and pressure-overload hypertrophy. Interstitial fibroblast proliferation and fibrosis are key contributors to the development of Heart failure, regardless of the etiology. Early detection and continued monitoring of fibrosis over the progression of Heart failure may facilitate a better understanding of the pathology of heart failure, help to identify patients who may benefit more from anti- fibrotic interventions, and allow for improved evaluation of the therapeutic effectiveness of different treatments in clinical trials. The activation of fibroblasts are reason for Myocardial fibrosis (MF). Activation of fibroblasts is considered the main mechanism of extracellular matrix remodeling in myocardial infarction, progressive heart failure. The fibroblast activation protein (FAP) expressed by myocardial activated fibroblasts is a serine protease belonging to the cell surface dipeptidyl peptidase (DPP) family, which could be seen as a marker for activated cardiac fibroblasts. Furthermore Somatostatin receptor (SST2) is released in response to vascular congestion and inflammatory and pro-fibrotic stimuli, and is a strong, independent predictor of mortality and heart failure (HF). FAP inhibitors (FAPIs) with an N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold were confirmed as promising inhibitors which combined low nanomolar FAP inhibition and high selectivity indices (>103) with respect to both the DPPs and prolyl oligopeptidase.Radiolabeled FAPI, has been used for non-invasive imaging of FAP expression.[68Ga]FAPI-04 has been successfully applied to the imaging of activated fibroblasts in patients with heart failure and myocardial infarction. However, whether a positron emission tomography/computed tomography (PET/CT) imaging scan of radioactive18F-ALF- FAPI-74 can assess activated fibroblasts in Heart failure remains unknown. In the current study, a Heart failure mouse model with aortic banding will be constructed , followed by [18F]AlF -FAPI-74 PET/CT (AlF = aluminum fluoride) and 18F-FET imaging to determine whether the tracer could be used to detect activated fibroblasts in mice with Heart failure and its mechanism by tracking SST2 receptor. The advantages of this model are that the mortality rate of the banding procedure is relatively low.

The animals are operated on once (primary operation) as stated in the "Sedation, analgesia and anaesthesia" section of the experiment. The experimental groups will be divided into control group sham operated mice as a control group and aortic-banded (AB) mice. Then animals will undergo the PET/CT In vivo imaging

We also use several alternative research methods, e.g. we work a lot with established cell lines and molecular biological methods, but the purpose of the mouse experiments is to study the function of this FAPI, SST2 receptor and integrin protein in intact living mammals. we must be careful not to draw conclusions from in vitro studies that may not reflect the reality in vivo. We shall use different PET tracers to evaluate complete physiological system including factors as biodistribution, PK/PD and target engagement.