Requirement of Pdgfrα+ cells for calvarial bone repair.

Platelet-derived growth factor receptor α (PDGFRα) is often considered as a general marker of mesenchymal cells and fibroblasts, but also shows expression in a portion of osteoprogenitor cells. Within the skeleton, Pdgfrα+ mesenchymal cells have been identified in bone marrow and periosteum of long bones, where they play a crucial role in participating in fracture repair. A similar examination of Pdgfrα+ cells in calvarial bone healing has not been examined. Here, we utilize Pdgfrα-CreERTM;mT/mG reporter animals to examine the contribution of Pdgfrα+ mesenchymal cells to calvarial bone repair through histology and single-cell RNA sequencing (scRNA-Seq). Results showed that Pdgfrα+ mesenchymal cells are present in several cell clusters by scRNA-Seq, and by histology a dramatic increase in Pdgfrα+ cells populated the defect site at early timepoints to give rise to healed bone tissue overtime. Notably, diphtheria toxin-mediated ablation of Pdgfrα reporter+ cells resulted in significantly impaired calvarial bone healing. Our findings suggest that Pdgfrα-expressing cells within the calvarial niche play a critical role in the process of calvarial bone repair.

Development of a novel radiofluorinated riboflavin probe for riboflavin receptor-targeting PET imaging.

Riboflavin receptor 3 (RFVT3) is a key protein in energetic metabolism reprogramming and is overexpressed in multiple cancers involved in malignant proliferation, angiogenesis, chemotherapy resistance, and immunosuppression. To enable non-invasive real-time quantification of RFVT3 in tumors, we sought to develop a suitable PET probe that would allow specific and selective RFVT3 imaging in vivo. A novel radiofluorinated riboflavin probe (18F-RFTA) based on riboflavin was synthesized and characterized in terms of radiochemical purity, hydrophilicity, binding affinity, and stability. Positron emission tomography (PET) imaging of 18F-RFTA was performed in U87MG tumor-bearing mice. Immunohistochemistry staining was carried out to determine the expression of RFVT3 in U87MG tumors. 18F-RFTA was characterized by high radiochemical purity and RFVT3 binding affinity, and remarkable stability in vitro and in vivo. Small-animal PET imaging with 18F-RFTA revealed significantly higher uptake in RFVT3-expressing U87MG tumors than in muscle. In conclusion, we have developed the first radiofluorinated riboflavin-based PET probe that is suitable for imaging RFVT3-positive tumors. The new target/probe system can be leveraged for extensive use in the diagnosis and treatment of RFVT3 overexpressing diseases, such as oncologic, cardiovascular, and neurodegenerative diseases.

Recent advances and applications of microspheres and nanoparticles in transarterial chemoembolization for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is a recommended treatment for patients suffering from intermediate and advanced hepatocellular carcinoma (HCC). As compared to the conventional TACE, drug-eluting bead TACE demonstrates several advantages in terms of survival, treatment response, and adverse effects. The selection of embolic agents is critical to the success of TACE. Many studies have been performed on the modification of the structure, size, homogeneity, biocompatibility, and biodegradability of embolic agents. Continuing efforts are focused on efficient loading of versatile chemotherapeutics, controlled sizes for sufficient occlusion, real-time detection intra- and post-procedure, and multimodality imaging-guided precise treatment. Here, we summarize recent advances and applications of microspheres and nanoparticles in TACE for HCC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Molecular Imaging of Tumor Microenvironment to Assess the Effects of Locoregional Treatment for Hepatocellular Carcinoma.

Liver cancer is one of the leading causes of cancer deaths worldwide. Among all primary liver cancers, hepatocellular carcinoma (HCC) is the most common type, representing 75%-85% of all primary liver cancer cases. Median survival following diagnosis of HCC is approximately 6 to 20 months due to late diagnosis in its course and few effective treatment options. Interventional therapy with minimal invasiveness is recognized as a promising treatment for HCC. However, due to the heterogeneity of HCC and the complexity of the tumor microenvironment, the long-term efficacy of treatment for HCC remains a challenge in the clinic. Tumor microenvironment, including factors such as hypoxia, angiogenesis, low extracellular pH, interstitial fluid pressure, aerobic glycolysis, and various immune responses, has emerged as a key contributor to tumor residual and progression after locoregional treatment for HCC. New approaches to noninvasively assess the treatment response and assist in the clinical decision-making process are therefore urgently needed. Molecular imaging tools enabling such an assessment may significantly advance clinical practice by allowing real-time optimization of treatment protocols for the individual patient. This review discusses recent advances in the application of molecular imaging technologies for noninvasively assessing changes occurring in the microenvironment of HCC after locoregional treatment.