Background: Angiogenesis is a process that many tumors depend on for growth, development, and metastasis. Vascular endothelial growth factor (VEGF) is one of the major players in tumor angiogenesis in several tumor types, including melanoma. VEGF inhibition is achieved by bevacizumab, a humanized monoclonal antibody that binds with high affinity to VEGF and prevents its function. In order to successfully enable in vivo VEGF expression imaging in a murine melanoma model, we previously labeled bevacizumab with [Tc]Tc. We observed that this was feasible, but it had prolonged blood circulation and delayed tumor uptake.
Objective: The aim of this study was to develop a radiolabeled Fab bevacizumab fragment, [Tc]Tc-HYNICFab( bevacizumab), for non-invasive VEGF expression molecular imaging.
Methods: Flow cytometry was used to examine VEGF presence in the murine melanoma cell line (B16-F10). Bevacizumab was digested with papain for six hours at 37°C to produce Fab(bevacizumab), which was then conjugated to NHS-HYNIC-Tfa for radiolabeling with [Tc]Tc. Stability and binding affinity assays were also evaluated. Biodistribution and single photon emission computed tomography/computed tomography (SPECT/CT) were performed at 1, 3, and 6 h (n = 4) after injection of [Tc]Tc-HYNIC-Fab(Bevacizumab) in normal and B16-F10 tumor-bearing C57Bl/6J mice.
Results: Using flow cytometry, it was shown that the B16-F10 murine melanoma cell line has intracellular VEGF expression. Papain incubation resulted in the complete digestion of bevacizumab with good purity and homogeneity. The radiolabeling yield of [Tc]Tc-HYNIC-Fab(bevacizumab) was 85.00 ± 6.06%, with a specific activity of 291.87 ± 18.84 MBq/mg (n=3), showing in vitro stability. Binding assays demonstrated significant intracellular in vitro VEGF expression. Fast blood clearance and high kidney and tumor uptake were observed in biodistribution and SPECT/CT studies.
Conclusions: We present the development and evaluation of [Tc]Tc-HYNIC-Fab(bevacizumab), a novel molecular VEGF expression imaging agent that may be used for precision medicine in melanoma and potentially in other VEGF-expressing tumors.
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http://dx.doi.org/10.2174/0118715206294297240805073550 | DOI Listing |
Diabetes
December 2024
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Advances in fundus imaging are revealing disruptions in the neurovascular unit in diabetic retinopathy (DR). In the era of anti-VEGF treatment, a thorough characterization of neurodegeneration is imperative until DR patients are sufficiently cured. Here we demonstrate that extracellular mitochondria exacerbate retinal pigment epithelium (RPE) degeneration and inflammation in DR.
View Article and Find Full Text PDFJ Chin Med Assoc
December 2024
Department of Stomatology, The Fourth Hospital of Hebei Medical University, Hebei Tumor Hospital, Hebei, China.
Background: To investigate the effect of nimotuzumab (N) combined with nab-paclitaxel, cisplatin, and fluorouracil (APF) neoadjuvant chemotherapy on the surgical margin.
Methods: 55 patients were divided into three groups: neoadjuvant chemotherapy and surgery group (G1, 15 cases), chemotherapy and surgery group (G2 group, 20 cases), and surgery group (G3 group, 20 cases). Tissue samples of the tumor core zone (P0), adjacent (P1, 3-5mm from tumor), distal adjacent (P2, 7-10mm from tumor), and surgical margin (P3, 15mm from tumor) were collected.
Prog Neurobiol
December 2024
Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. Electronic address:
Inflammation is a major mechanism of photoreceptor cell death in the retina during macular degeneration leading to the blindness. In this study, we investigated the role of the kinase molecule Zap70, which is an inflammatory regulator of the systemic immune system, to elucidate the control mechanism of inflammation in the retina. We observed activated microglial cells migrated and populated the retinal layer following blue LED-induced photoreceptor degeneration and activated microglial cells in the LED-injured retina expressed Zap70, unlike the inactive microglial cells in the normal retina.
View Article and Find Full Text PDFExp Neurol
December 2024
Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata 951-8585, Japan. Electronic address:
Background: Despite advances in reperfusion therapies, ischemic stroke remains a major cause of long-term disability due to residual hypoxic lesions persisting after macrovascular reperfusion. These residual hypoxic lesions, caused by microvascular dysfunction, represent an important therapeutic target. We previously demonstrated that oxygen-glucose-deprived peripheral blood mononuclear cells (OGD-PBMCs) migrate to ischemic brain regions and promote functional recovery after stroke.
View Article and Find Full Text PDFBiomed Eng Online
December 2024
Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Background: Despite the development of various therapeutic approaches over the past decades, the treatment of glioblastoma multiforme (GBM) remains a major challenge. The extracellular adenosine-generating enzyme, CD73, is involved in the pathogenesis and progression of GBM, and targeting CD73 may represent a novel approach to treat this cancer. In this study, three-dimensional culture systems based on three hydrogel compositions were characterized and an optimal type was selected to simulate the GBM microenvironment.
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