Gallium 68–labeled fibroblast-activation protein inhibitor PET/CT may outperform fluorine 18–labeled fluorodeoxyglucose PET/CT in staging lung cancer, particularly in the detection of metastasis to... Background Gallium 68 (68Ga)–labeled fibroblast-activation protein inhibitor (FAPI) has recently been introduced as a promising tumor imaging agent. Purpose To compare 68Ga-FAPI PET/CT with fluorin...

Due to tumor heterogeneity and complex tumor–stromal interactions in multicellular systems, the efficiency of monospecific tracers for tumor diagnosis and therapy is currently limited. In light of the evidence of prostate-specific membrane antigen (PSMA) overexpression in tumor cells and fibroblast activation protein (FAP) upregulation in the tumor stroma, heterodimer dual targeting PSMA and FAP may have the potential to improve tumor diagnosis. Herein, we described the radiosynthesis, in vitro characterization, and micro-PET/CT imaging of two novel ¹⁸F-labeled bispecific PSMA/FAP heterodimers. ¹⁸F-labeled heterodimers showed high specificity and affinity targeting to PSMA and FAP in vitro and in vivo. Compared with the monospecific tracers [¹⁸F]AlF-PSMA-BCH and [¹⁸F]FAPI-42, both ¹⁸F-labeled heterodimers exhibited better tumor uptake in tumor-bearing mice. Their favorable characterizations such as convenient synthesis, high tumor uptake, and favorable pharmacokinetic profile could lead to their future applications as bispecific radiotracers for clinical cancer imaging.

To explore the expression and prognosis of Fc fragment of IgG low affinity IIb receptor (FCGR2B) in glioma and its relationship with immune microenvironment, so as to provide potential molecular targets for the treatment of glioma. We analyzed the gene expression of FCGR2B using the Cancer Genome Atlas database, Chinese Glioma Genome Atlas, Gene Expression Omnibus database and other glioma related databases. Moreover, we generated survival receiver operating characteristic curve, carried out univariate and multivariate Cox analysis and nomograph construction, and analyzed the relationship between FCGR2B and prognosis. According to the median of FCGR2B gene expression value, the differential expression analysis was carried out by high and low grouping method, and the gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis enrichment analysis were carried out to explore the possible mechanism. Then, the correlation between immune score of glioma and prognosis, World Health Organization grade and FCGR2B expression was analyzed. Finally, the correlation between FCGR2B expression and the proportion of tumor infiltrating immune cells, immune checkpoints, tumor mutation load and immune function was analyzed. The expression of FCGR2B in gliomas was higher than that in normal tissues and was associated with poor prognosis. Independent prognostic analysis showed that FCGR2B was an independent prognostic factor for glioma. The analysis of gene ontology and gene set enrichment analysis showed that FCGR2B was closely related to immune-related functions. The analysis of immune scores and prognosis, World Health Organization grade and FCGR2B expression in gliomas indicated that patients with high immune scores had significantly poorer overall survival and higher tumor pathological grade. In addition, immune scores were significantly positively correlated with the expression of FCGR2B. The analysis of tumor infiltrating immune cells suggested that the expression level of FCGR2B affected the immune activity of TME. In addition, the expression of FCGR2B was positively correlated with almost all immune checkpoint molecules including CD28, CD44, TNFSF14, PDCD1LG2, LAIR1, and CD48 and was significantly positively correlated with tumor mutation load. All immunobiological functions of the high expression group of FCGR2B were significantly inhibited. FCGR2B may play an important role in the occurrence, development and invasion of tumor by influencing the tumor microenvironment of immunosuppression. FCGR2B may be an important target for the treatment of glioma.

Background: Hepatic fibrosis is a progressive disease, which is reversible in the early stages. The current monitoring methods have notable limitations that pose a challenge to early detection. In this study, we evaluated the utility of [¹⁸F]AlF-ND-bisFAPI positron emission tomography imaging of fibroblast activation protein (FAP) to monitor the progression of liver fibrosis. Methods: Two mouse models of liver fibrosis were established by bile duct ligation and carbon tetrachloride administration, respectively. Positron emission tomography imaging was performed with the FAP-specific radiotracer [¹⁸F]AlF-ND-bisFAPI for the evaluation of rat HSCs and mouse models of fibrosis and combined with histopathology, immunohistochemical staining, and immunoblotting to elucidate the relationships among radioactivity uptake, FAP levels, and liver fibrosis progression. Furthermore, [¹⁸F]AlF-ND-bisFAPI autoradiography was performed to assess tracer binding in liver sections from patients with varying degrees of liver fibrosis. Results: Cell experiments demonstrated that [¹⁸F]AlF-ND-bisFAPI uptake was specific in activated HSCs. Compared with control mice, [¹⁸F]AlF-ND-bisFAPI uptake in livers increased in the early stages of fibrosis and increased significantly further with disease progression. Immunohistochemistry and western blot analyses demonstrated that FAP expression increased with fibrosis severity. In accordance with the findings in animal models, ex vivo autoradiography on human fibrotic liver sections showed that radioactivity increased as fibrosis progressed from mild to severe. Conclusions: [¹⁸F]AlF-ND-bisFAPI positron emission tomography imaging is a promising noninvasive method for monitoring the progression of liver fibrosis.

A direct electrolysis protocol for difluorination and azo-fluorination of gem -difluorostyrenes was achieved involving Et ₃ N·3HF as fluorine source. The electrochemical reduction of the benzyl C–F bond was also achieved.