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Frontiers in Oncology · 2022 · IF 5.738

Evaluation of a CD13 and Integrin αvβ3 Dual-Receptor Targeted Tracer 68Ga-NGR-RGD for Ovarian Tumor Imaging: Comparison With 18F-FDG

Long Yu,Shao Fuqiang,Ji Hao,Song Xiangming,Lv Xiaoying,Xia Xiaotian,Liu Qingyao,Zhang Yongxue,Zeng Dexing,Lan Xiaoli,Gai Yongkang

Ovarian cancer has the highest mortality rate of gynecologic malignancy. 18F-FDG positron emission tomography (PET) adds an important superiority over traditional anatomic imaging modalities in oncological imaging but has drawbacks including false negative results at the early stage of ovarian cancer, and false positives when inflammatory comorbidities are present. Aminopeptidase N (APN, also known as CD13) and integrin αvβ3 are two important targets overexpressed on tumor neo-vessels and frequently on ovarian cancerous cells. In this study, we used subcutaneous and metastatic models of ovarian cancer and muscular inflammation models to identify 68Ga-NGR-RGD, a heterodimeric tracer consisting of NGR and RGD peptides targeting CD13 and integrin αvβ3, respectively, and compared it with 18F-FDG. We found that 68Ga-NGR-RGD showed greater contrast in SKOV3 and ES-2 tumors than 18F-FDG. Low accumulation of 68Ga-NGR-RGD but avid uptake of 18F-FDG were observed in inflammatory muscle. In abdominal metastasis models, PET imaging with 68Ga-NGR-RGD allowed for rapid and clear delineation of both peritoneal and liver metastases (3-6 mm), whereas, 18F-FDG could not distinguish the metastasis lesions due to the relatively low metabolic activity in tumors and the interference of intestinal physiological 18F-FDG uptake. Due to the high tumor-targeting efficacy, low inflammatory uptake, and higher tumor-to-background ratios compared to that of 18F-FDG, 68Ga-NGR-RGD presents a promising imaging agent for diagnosis, staging, and follow-up of ovarian tumors.

CAS / MDL: 8006-64-2
研究领域: 肿瘤学 · 医学影像学 · 分子生物学 · 癌症研究
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Advanced Optical Materials · 2022 ·Vol. 10 ·期 14 ·2102709 · IF 10.05

An APN-Activated Chemiluminescent Probe for Image-Guided Surgery of Malignant Tumors

Yinghua Liu,Jianfeng Zeng,Qing Li,Minqian Miao,Zhuorun Song,Min Zhao,Qingqing Miao,Mingyuan Gao

Developing smart molecular probes for assisting surgeons to precisely detect cancerous tissues and to completely remove all of them during the surgery is urgently required. Conventional fluorescent probes allow for tumor detection but with limited signal-to-noise ratio. Herein, an aminopeptidase N/CD13 (APN)-activated chemiluminescent probe (APN-ACLP) is reported for sensitive imaging and precise resection of malignant tumors. The APN-ACLP probe is based on acryl-substituted phenoxy-dioxetane that is coupled with an APN-cleavable substrate via a self-immolative linker. Upon activation by APN through specific hydrolysis reaction, APN-ACLP generates spontaneously chemiluminescence signal, which offers a possibility to sensitively search tumors by simply spraying APN-ACLP on the suspicious sites. Animal imaging studies reveal that a sufficient signal contrast between the cancerous tissues and the normal counterparts can be achieved within 5 min, which can allow for rapid detection and surgical resection of tumors, particularly tiny metastatic lesions in mice model, under the guidance of chemiluminescence imaging, well manifesting its potential for image-guided surgery of malignant tumors.

CAS / MDL: 58970-76-6
研究领域: 医学成像 · 肿瘤学 · 生物医学工程 · 分子生物学
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PLoS One · 2024 ·Vol. 19 ·期 8 ·e0308132 · IF 2.9

Oligodendroglia-to-pericyte conversion after lipopolysaccharide exposure is gender-dependent

Qingting Yu,Linyuan Zhang,Ting Xu,Jiapeng Shao,Falei Yuan,Zuisu Yang,Yuncheng Wu,Haiyan Lyu

To investigate the sex-dependent differentiation of Sox10 cells and their response to pathological conditions such as lipopolysaccharide (LPS) exposure or ischemia, we utilized Sox10 Cre-ER T2 , tdTomato mice. Tamoxifen administration induced the expression of red fluorescent protein (RFP) in these cells, facilitating their subsequent tracking and analysis after LPS injection and ischemia via immunofluorescence staining. Propidium iodide (PI) was injected to label necrotic cells following LPS administration. We found that the conversion of Sox10 cells to pericytes in female mice was significantly higher than in male mice, especially in those exposed to LPS. After LPS injection, the number of PI + necrotic cells were significantly greater in females than in males. Moreover, RFP + cells did not co-localize with glial fibrillary acidic protein (GFAP) or cluster of differentiation 11b (CD11b). Similarly, after brain ischemia, RFP + cells did not express cluster of differentiation 13 (CD13), neuronal nuclei (NeuN), GFAP, or ionised calcium binding adaptor molecule 1 (Iba-1). These findings indicate that the conversion of Sox10 cells to pericytes following LPS exposure is sex-dependent, with neither male nor female groups showing differentiation into other cell types after LPS exposure or under ischemic conditions. The differences in LPS-induced necrosis of pericytes between sexes may explain the variations in the conversion of Sox10 cells to pericytes in both sexes.

研究领域: 神经科学 · 免疫学 · 细胞生物学
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