Abstract:Background:
FAP (fibroblast activation protein) plays an important role in cardiac wound healing and remodeling. Although initially developed as a theranostic ligand for metastasized cancer, FAPI (FAP inhibitor) tracers have recently been used to study cardiac remodeling following myocardial infarction in small-animal models. The aim of the study was to evaluate the activity of FAP via FAPI–positron emission tomography–computed tomography scans in human hearts.
Met… Show more
“…Increased FAP has reportedly been found in refractory rheumatoid arthritis [20]. Besides renal brosis, high intake of FAPI has been found in benign diseases such as liver brosis, arthritis, cardiovascular disease, Crohn's bowel disease, idiopathic retroperitoneal brosis, pancreatitis, and osteophytes [21][22][23][24][25][26][27][28]. The diagnostic utility of [ 68 Ga]Ga-FAPIs needs further exploration.…”
Renal brosis is a pathological state in the progression of chronic kidney disease. Early detection and treatment are vital to prolong the survival of patients. Renal puncture examination represents the gold standard examination method for renal brosis, but it has several limitations. This study aims to evaluate the diagnostic performance of a novel PET radiotracer, [ 68 Ga]Ga-broblast activation protein inhibitor (FAPI)-04, which speci cally images broblast activation protein (FAP) expression for renal brosis.
MethodsAll patients underwent renal puncture before receiving [ 68 Ga]Ga-FAPI-04 PET/CT imaging. They then underwent [ 68 Ga]Ga-FAPI-04 PET/CT and immunochemistry examinations, and the data obtained were analyzed.
ResultsThe [ 68 Ga]Ga-FAPI-04 PET/CT examination results showed that almost all patients (12/13) exhibited increased radiotracer uptake. The maximum standardized uptake value (SUVmax) in patients with mild, moderate, and severe brosis was 3.92±1.50, 5.98±1.6, and 7.67±2.23, respectively.
ConclusionCompared with renal puncture examination, non-invasive imaging of FAP expression through [ 68 Ga]Ga-FAPI-04 PET/CT can quickly show the patient's bilateral kidney condition with high sensitivity. This can facilitate the evaluation of the patient's disease progression, diagnosis, and the development of a treatment plan.
“…Increased FAP has reportedly been found in refractory rheumatoid arthritis [20]. Besides renal brosis, high intake of FAPI has been found in benign diseases such as liver brosis, arthritis, cardiovascular disease, Crohn's bowel disease, idiopathic retroperitoneal brosis, pancreatitis, and osteophytes [21][22][23][24][25][26][27][28]. The diagnostic utility of [ 68 Ga]Ga-FAPIs needs further exploration.…”
Renal brosis is a pathological state in the progression of chronic kidney disease. Early detection and treatment are vital to prolong the survival of patients. Renal puncture examination represents the gold standard examination method for renal brosis, but it has several limitations. This study aims to evaluate the diagnostic performance of a novel PET radiotracer, [ 68 Ga]Ga-broblast activation protein inhibitor (FAPI)-04, which speci cally images broblast activation protein (FAP) expression for renal brosis.
MethodsAll patients underwent renal puncture before receiving [ 68 Ga]Ga-FAPI-04 PET/CT imaging. They then underwent [ 68 Ga]Ga-FAPI-04 PET/CT and immunochemistry examinations, and the data obtained were analyzed.
ResultsThe [ 68 Ga]Ga-FAPI-04 PET/CT examination results showed that almost all patients (12/13) exhibited increased radiotracer uptake. The maximum standardized uptake value (SUVmax) in patients with mild, moderate, and severe brosis was 3.92±1.50, 5.98±1.6, and 7.67±2.23, respectively.
ConclusionCompared with renal puncture examination, non-invasive imaging of FAP expression through [ 68 Ga]Ga-FAPI-04 PET/CT can quickly show the patient's bilateral kidney condition with high sensitivity. This can facilitate the evaluation of the patient's disease progression, diagnosis, and the development of a treatment plan.
“…Derived from the pathomechanism, myocarditis in general and fibrosis in terms of cardiomyopathy might be detectable by FAPI PET/CT, as they are based on inflammation and tissue remodeling. Recently, it was shown that diabetes is associated with elevated tracer enrichment in FAPI PET/CT in the heart ( 17 ). This was associated with an enrichment of tracer accumulation within all segments of the left ventricle, whereas patients with ICI-associated myocarditis revealed a localized enrichment.…”
Objective: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-associated myocarditis.Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n = 23) to three patients with suspected ICI-associated myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. All three patients' myocardial biopsies were examined for inflammatory cells.Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1,771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients' FAPI PET/CTs showed cardiac enrichment of the marker which was less distinct or absent in patients receiving ICIs without any signs of immunological adverse effects or cardiac impairment (n = 23) [Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)].Conclusions: Apart from the successful implementation of ICIs in oncological treatments, ICI-associated myocarditis is still a challenging adverse effect. FAPI PET/CT may be used in order to identify affected patients at an early stage. Moreover, when integrated into cancer stage diagnostics, it contributes to cardiac risk stratification besides biomarker, ECG and echocardiography.
“…High left ventricular FAP signal intensities as measured by positron-emission-tomography are associated with cardiovascular and metabolic risk factors such as hypertension, diabetes mellitus and obesity [ 35 ]. Moreover, advances have been made using therapies depleting FAP cells to treat cancer disease, which could potentially affect the heart [ 16 , 36 ].…”
Introduction
Regulating excessive activation of fibroblasts may be a promising target to optimize extracellular matrix deposition and myocardial stiffness. Fibroblast activation protein alpha (FAP) is upregulated in activated fibroblasts after myocardial infarction (MI), and alters fibroblast migration in vitro. We hypothesized that FAP depletion may have a protective effect on left ventricular (LV) remodeling after MI.
Materials and methods
We used the model of chronic MI in homozygous FAP deficient mice (FAP-KO, n = 51) and wild type mice (WT, n = 55) to analyze wound healing by monocyte and myofibroblast infiltration. Heart function and remodeling was studied by echocardiography, morphometric analyses including capillary density and myocyte size, collagen content and in vivo cell-proliferation. In non-operated healthy mice up to 6 months of age, morphometric analyses and collagen content was assessed (WT n = 10, FAP-KO n = 19).
Results
Healthy FAP-deficient mice did not show changes in LV structure or differences in collagen content or cardiac morphology. Infarct size, survival and cardiac function were not different between FAP-KO and wildtype mice. FAP-KO animals showed less LV-dilation and a thicker scar, accompanied by a trend towards lower collagen content. Wound healing, assessed by infiltration with inflammatory cells and myofibroblasts were not different between groups.
Conclusion
We show that genetic ablation of FAP does not impair cardiac wound healing, and attenuates LV dilation after MI in mice. FAP seems dispensable for normal cardiac function and homeostasis.
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