Background Myocardial fibrosis contributes to adverse cardiovascular events in hypertrophic cardiomyopathy (HCM). Purpose To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/CT imaging and its relationship with the risk of sudden cardiac death (SCD) in HCM. Materials and Methods In this prospective study from July 2021 to January 2022, participants with HCM and healthy control participants underwent cardiac fluorine 18 (F)-labeled FAPI PET/CT imaging. Myocardial FAPI activity was quantified as intensity (target-to-background uptake ratio), extent (the percent of FAPI-avid myocardium of the left ventricle [LV]), and amount (the percent of FAPI-avid myocardium of LV × target-to-background ratio). Regional wall thickness was analyzed at cardiac MRI. The 5-year SCD risk score was calculated from the 2014 European Society of Cardiology guidelines. Univariable and multivariable linear regression analyses were used to identify factors related to the FAPI amount. The correlation between FAPI amount and 5-year SCD risk was explored. Results Fifty study participants with HCM (mean age, 43 years ± 13 [SD]; 32 men) and 22 healthy control participants (mean age, 45 years ± 17; 14 men) were included. All participants with HCM had intense and inhomogeneous cardiac FAPI activity in the LV myocardium that was higher than that in healthy control participants (median target-to-background ratio, 8.8 vs 2.1, respectively; < .001). In HCM, more segments with FAPI activity were detected than the number of hypertrophic segments (median, 14 vs five, respectively; < .001); 84% of nonhypertrophic segments showed FAPI activity. Log-transformed FAPI amount had a positive relationship with log-transformed -terminal probrain natriuretic peptide, high-sensitive troponin I, and left atrial diameter and a negative relationship with LV ejection fraction -score. Degree of FAPI activity positively correlated with the 5-year SCD risk score ( = 0.32; = .03). Conclusion Fibroblast activation protein inhibitor (FAPI) PET/CT imaging indicated intense and heterogeneous activity in hypertrophic cardiomyopathy, and FAPI uptake was associated with 5-year risk of sudden cardiac death. © RSNA, 2022
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http://dx.doi.org/10.1148/radiol.221052 | DOI Listing |
Nat Commun
January 2025
Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, PR China.
Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance (ABC) effect. We design three ionizable oligomers (IOs) that, with polylactide-polyethylene glycol (PLA-PEG), form a potential siRNA delivery system, named Ionizable Polymeric Micelles (IPMs). The siRNA encapsulated IPMs escape from lysosomes upon cellular uptake, and silence the target gene.
View Article and Find Full Text PDFJ Nucl Med
January 2025
Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;
Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof of principle, we tested whether this strategy of radionuclide-induced drug engagement for release (RAiDER) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing off-target exposure to activated chemotherapy.
View Article and Find Full Text PDFJ Nucl Med
January 2025
Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou, China; and
The purpose of this study was to investigate the feasibility of using F-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in assessing the fibrotic remodeling of the pulmonary artery (PA) and the right ventricle (RV) in pulmonary arterial hypertension (PAH). In a rat model of monocrotaline-induced PAH, rats were euthanized at different time points for tissue analysis (fibroblast activation protein immunofluorescence and Masson's trichrome staining) after completing F-FAPI PET/CT and hemodynamic measurements. Thirty-eight PAH patients were enrolled to participate in F-FAPI PET/CT imaging, with right heart catheterization and echocardiography performed within 1 wk to assess pulmonary hemodynamics and cardiac function.
View Article and Find Full Text PDFMol Pharm
December 2024
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
Fibroblast activation protein inhibitors (FAPIs) labeled with gallium-68 and lutetium-177 show potential for use in the diagnosis and treatment of various cancers expressing FAP. However, Lu-labeled FAPIs often exhibit short tumor retention time, limiting their therapeutic applications. To improve tumor retention, we synthesized three radiolabeled dimeric FAPIs, [F], [Cu], and [Ga].
View Article and Find Full Text PDFEJNMMI Res
December 2024
Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Centre Rotterdam, Rotterdam, GD, 3015, The Netherlands.
Background: Fibroblast activation protein (FAP) is an attractive target for cancer theranostics. Although FAP-targeted nuclear imaging demonstrated promising clinical results, only sub-optimal results are reported for targeted radionuclide therapy (TRT). Preclinical research is crucial in selecting promising FAP-targeted radiopharmaceuticals and for obtaining an increased understanding of factors essential for FAP-TRT improvement.
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