Research
·
2022
·
IF 11.036
Song Liu,Guanghui Li,Lei Ding,Jin Ding,Qian Zhang,Dan Li,Xingguo Hou,Xiangxing Kong,Jing Zou,Shiming Zhang,Hongbin Han,Yakun Wan,Zhi Yang,Hua Zhu
Due to the rapid spread of coronavirus disease 2019 (COVID-19), there is an urgent requirement for the development of additional diagnostic tools for further analysis of the disease. The isolated nanobody Nb11-59 binds to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) with high affinity to neutralize the virus and block the angiotensin-converting enzyme 2- (ACE2-) RBD interaction. Here, we introduce a novel nanobody-based radiotracer named 68Ga-Nb1159. The radiotracer retained high affinity for the RBD and showed reliable radiochemical characteristics both in vitro and in vivo. Preclinical positron emission tomography (PET) studies of 68Ga-Nb1159 in mice revealed its rapid clearance from circulation and robust uptake into the renal and urinary systems. Fortunately, 68Ga-Nb1159 could specifically reveal the distribution of the RBD in mice. This study also helped to evaluate the pharmacodynamic effects of the neutralizing nanobody. Moreover, 68Ga-Nb1159 may be a promising tool to explore the distribution of the RBD and improve the understanding of the virus. In particular, this study identified a novel molecular radioagent and established a reliable evaluation method for specifically investigating the RBD through noninvasive and visual PET technology.
研究领域:
医学影像学
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病毒学
·
药理学
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DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Di Hua,Hongjie Xi,Quan Xie,Shuyue Cai,Yuxuan Zhou,Xin Hu,Ling Qiu,Jianguo Lin
Legumain is overexpressed in diverse tumors, serving as a significant tumor biomarker. Our study aimed to develop a new positron emission tomography (PET) probe [ 68 Ga]Ga-NOTA-SF-AANM for imaging the expression level of legumain in vivo . The radio-labeling of [ 68 Ga]Ga-NOTA-SF-AANM was accomplished within 15 min. The probe has good stability in vitro . NOTA-SF-AANM exhibited rapid response to recombinant human legumain enzyme, enabling intramolecular condensation cyclization. Cellular uptake and lysosomal co-localization experiments demonstrated that the probe was able to differentiate specifically between MDA-MB-468 and PC-3 cancer cells with varying degrees of legumain expression. PET imaging displayed a significant and persistent signal (3.59 ± 0.30 %ID/mL at 60 min) in MDA-MB-468 tumors, while PC-3 tumors exhibited lower radioactivity (1.08 ± 0.35 %ID/mL at 60 min), further validating the specific targeting of [ 68 Ga]Ga-NOTA-SF-AANM towards legumain. [ 68 Ga]Ga-NOTA-SF-AANM is a promising tool for precise diagnosis of legumain-related diseases due to its advantages in radio-labeling and accurate monitoring of legumain expression levels.
研究领域:
医学影像学
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分子生物学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2023
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IF 4.7
Liu Zhenfeng,Wen Guanghua,Huang Yuqiao,Dong Yanzhao,Wang Zewei,Alhaskawi Ahmad,Zhang Shuyi,Wang GuoLin,Ye Qianni,Zhou Haiying,Lu Hui,Dong Mengjie
Background: The cell adhesion molecule (CAM) N-cadherin has become an important target for tumor therapy. The N-cadherin antagonist, ADH-1, exerts significant antitumor activity against N-cadherin-expressing cancers.Methods: In this study, [18F]AlF-NOTA-ADH-1 was radiosynthesized. An in vitro cell binding test was performed, and the biodistribution and micro-PET imaging of the probe targeting N-cadherin were also studied in vivo.Results: Radiolabeling of ADH-1 with [18F]AlF achieved a yield of up to 30% (not decay-corrected) with a radiochemical purity of >97%. The cell uptake study showed that Cy3-ADH-1 binds to SW480 cells but weakly binds to BXPC3 cells in the same concentration range. The biodistribution results demonstrated that [18F]AlF-NOTA-ADH-1 had a good tumor/muscle ratio (8.70±2.68) in patient-derived xenograft (PDX) tumor xenografts but a lower tumor/muscle ratio (1.91±0.69) in SW480 tumor xenografts and lowest tumor/muscle ratio (0.96±0.32) in BXPC3 tumor xenografts at 1 h post-injection (p.i.) These findings were in accordance with the immunohistochemistry results. The micro PET imaging results revealed good [18F]AlF-NOTA-ADH-1 tumor uptake in pancreatic cancer PDX xenografts with strong positive N-calcium expression, while lower tumor uptake in SW480 xenografts with positive expression of N-cadherin, and significantly lower tumor uptake in BXPC3 xenografts with low expression of N-cadherin, which was consistent with the biodistribution and immunohistochemistry results. The N-cadherin-specific binding of [18F]AlF-NOTA-ADH-1 was further verified by a blocking experiment involving coinjection of a non radiolabeled ADH-1 peptide, resulting in a significant reduction in tumor uptake in PDX xenografts and SW480 tumor.Conclusion: [18F]AlF-NOTA-ADH-1 was successfully radiosynthesized, and Cy3-ADH-1 showed favorable N-cadherin-specific targeting ability by in vitro data. The biodistribution and microPET imaging of the probe further showed that [18F]AlF-NOTA-ADH-1 could discern different expressions of N-cadherin in tumors. Collectively, the findings demonstrated the potential of [18F]AlF-NOTA-ADH-1 as a PET imaging probe for non-invasive evaluation of the N-cadherin expression in tumors.
研究领域:
医学影像学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL INVESTIGATION
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2025
·Vol. 135
·期 6
·
IF 13.6
Lei Xia,Yan Wu,Yanan Ren,Zhen Wang,Nina Zhou,Wenyuan Zhou,Lixin Zhou,Ling Jia,Chengxue He,Xiangxi Meng,Hua Zhu,Zhi Yang
BACKGROUND. B7H3, also known as CD276, is notably overexpressed in various malignant tumor cells in humans, with extremely high expression rates. The development of a radiotracer that targets B7H3 may provide a universal tumor-specific imaging agent and allow the noninvasive assessment of the whole-body distribution of B7H3-expressing lesions.
METHODS. We enhanced and optimized the structure of an affibody (ABY) that targets B7H3 to create the radiolabeled radiotracer [68Ga]Ga-B7H3-BCH, and then, we conducted both foundational experiments and clinical translational studies.
RESULTS. [68Ga]Ga-B7H3-BCH exhibited high affinity (equilibrium dissociation constant [KD] = 4.5 nM), and it was taken up in large amounts by B7H3-transfected cells (A549CD276 and H1975CD276 cells); these phenomena were inhibited by unlabeled precursors. Moreover, PET imaging of multiple xenograft models revealed extensive [68Ga]Ga-B7H3-BCH uptake by tumors. In a clinical study including 20 patients with malignant tumors, the [68Ga]Ga-B7H3-BCH signal aggregated in both primary and metastatic lesions, surpassing fluorine-18 fluorodeoxyglucose (18F-FDG) in overall diagnostic efficacy for tumors (85.0% vs. 81.7%), including differentiated hepatocellular and metastatic gastric cancers. A strong correlation between B7H3 expression and [68Ga]Ga-B7H3-BCH uptake in tumors was observed, and B7H3 expression was detected with 84.38% sensitivity and 100% specificity when a maximum standardized uptake value (SUVmax) of 3.85 was set as the cutoff value. Additionally, B7H3-specific PET imaging is expected to predict B7H3 expression levels in tumor cells, intratumoral stroma, and peritumoral tissues.
CONCLUSION. In summary, [68Ga]Ga-B7H3-BCH has potential for the noninvasive identification of B7H3 expression in systemic lesions in patients with malignant tumors. This agent has prospects for improving pretreatment evaluation, predicting therapeutic responses, and monitoring resistance to therapy in patients with malignancies.
TRIAL REGISTRATION. ClinicalTrials.gov NCT06454955.
FUNDING. This research was financially supported by the Natural Science Foundation of Beijing Municipality (no. 7242266), the National Natural Science Foundation of China (no. 82202201), and the Young Elite Scientists Sponsorship Program by China Association for Science and Technology (CAST) (no. YESS20220230).
研究领域:
肿瘤学
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分子成像
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核医学
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诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Jingyao Gong,Yunlong Li,Hui Di,Jiamin Li,Junming Dong,Congjie He,Peng Cao,Huiming Cai,Jian He,Yiqing Wang
Combination of PET and optical imaging techniques holds significant potential for complete tumor resection to optimize patient outcomes. In this study, we combined two lapatinib-based molecular probes for detecting HER2-overexoression tumors through PET and near-infrared (NIR) fluorescence imaging. HER2 receptor had been confirmed to be overexpressed in many types of tumors and had become a specific target for molecular imaging. The radiolabeled probe [ 68 Ga] Ga-NOTA-lapatinib demonstrated superior imaging performance in micro-PET scans, achieving clear differentiation of subcutaneous tumors from adjacent tissues. Complementarily, the NIR fluorescent probe LP-S exhibited prolonged tumor retention (>72 h) with distinct signal demarcation between malignant and normal tissues in ex vivo analyses. Fluorescence microscopy further validated specific intra-tumoral accumulation of the probe at cellular resolution. This synchronized dual-probe strategy, leveraging identical targeting moieties, established a robust platform for multimodality cancer imaging that bridges preoperative detection with intraoperative visualization.
研究领域:
医学影像学
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分子生物学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Lixin Ding,Qian Guo,Ya’nan Ren,Pei Wang,Yongxiang Pan,Jin Ding,Feng Wang,Zhi Yang,Hua Zhu
Extracellular vesicles (EVs) act as carriers that transfer molecules between donor and recipient cells, thereby altering the phenotype and function of the latter. EVs derived from mesenchymal stem cells (MSCs) inherit the homing ability of their parent cells to tumor sites. We speculate that MSC-derived EVs labeled with the isotope zirconium-89 ([89Zr]Zr) will accumulate within tumors and have the potential for tumor location via positron emission tomography (PET) imaging. Here, as a proof of concept, we used [89Zr]Zr-labeled human umbilical cord MSC (hucMSC)-derived EVs to characterize the homing of EVs to tumor regions via PET imaging. The uptake of [89Zr]Zr-DFO-hucMSC-EVs by 4T1, H292, and FaDu cells increased in a time-dependent manner. [89Zr]Zr-DFO-hucMSC-EVs were rapidly cleared from the blood circulation, showing a 2-phase exponential decay with a biodistribution half-life of 0.46 h and an elimination-phase half-life of 11.87 h. At 24 h postinjection, [89Zr]Zr-DFO-hucMSC-EVs were mainly distributed in the liver (10.39 ± 0.52%ID/g) and, to a lesser extent, in the spleen (9.87 ± 0.87%ID/g). PET imaging in tumor-bearing mouse models revealed persistently high tumor accumulation. The projected effective dose for an adult human female was low and was 0.084 mSv/MBq. There was no obvious normal tissue toxicity following the administration of excessive radioactivity. In summary, these studies demonstrate the potential feasibility of using the [89Zr]Zr-DFO-hucMSC-EV tracer for noninvasive visualization of tumor lesions.
研究领域:
医学影像学
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细胞生物学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2022
·Vol. 15
·期 5
·513
·
IF 5.215
Ya’nan Ren,Teli Liu,Chen Liu,Xiaoyi Guo,Feng Wang,Hua Zhu,Zhi Yang
Prostate-specific membrane antigen (PSMA) is an ideal target for the diagnosis and treatment of prostate cancer. Due to the short half-life in blood, small molecules/peptides are rapidly cleared by the circulatory system. Prolonging the half-life of PSMA probes has been considered as an effective strategy to improve the tumor detection. Herein, we reported a64Cu-labeled PSMA tracer conjugating with maleimidopropionic acid (MPA),64Cu-PSMA-CM, which showed an excellent ability to detect PSMA-overexpressing tumors in delayed time. Cell experiments in PSMA-positive 22Rv1 cells, human serum albumin binding affinity, and micro-PET imaging studies in 22Rv1 model were performed to investigate the albumin binding capacity and PSMA specificity. Comparisons with64Cu-PSMA-BCH were performed to explore the influence of MPA on the biological properties.64Cu-PSMA-CM could be quickly prepared within 30 min. The uptake of64Cu-PSMA-CM in 22Rv1 cells increased over time and it could bind to HSA with a high protein binding ratio (67.8 ± 1.5%). When compared to64Cu-PSMA-BCH,64Cu-PSMA-CM demonstrated higher and prolonged accumulation in 22Rv1 tumors, contributing to high tumor-to-organ ratios. These results showed that64Cu-PSMA-CM was PSMA specific with a higher tumor uptake, which demonstrated that MPA is an optional strategy for improving the radioactivity concentration in PSMA-expressing tumors and for developing the ligands for PSMA radioligand therapy.Keywords:PSMA;prostate cancer;copper radioisotopes;maleimidopropionic acid;PET imaging
研究领域:
医学影像学
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肿瘤学
·
放射化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Lei Xia,Chengxue He,Yanhui Guo,Xiangxi Meng,Teli Liu,Xiaoxia Xu,Xiaoyi Guo,Feng Wang,Nan Li,Hua Zhu,Zhi Yang
Programmed death ligand 1 (PDL1) is a specific molecular target for the diagnosis and immunotherapy of solid tumors. PET imaging can be used for noninvasive assessments of PDL1 expression in tumors to aid in therapy selection. The most frequently reported small-molecule radiotracer of PDL1 is limited by low imaging specificity, short residence time, and singular functionality. Here, we combined a biocompatible melanin nanoprobe with the PDL1-binding peptide WL12 to construct a novel radiotracer, 124I-WPMN, to enhance PDL1 targeting. The radiochemical purity of 124I-WPMN was >95%, and uptake in A549PDL1 cells was 1.49 ± 0.08% at 2 h. The uptake was blocked by WL12 (0.39 ± 0.03%, P < 0.0001). This novel radiotracer showed a higher affinity for PDL1 (Kd = 18.5 nM) than 68Ga-NOTA-WL12 (Kd = 24.0 nM). Micro-PET/CT imaging demonstrated specific uptake and a high signal-to-noise ratio in an A549PDL1 xenograft mouse model with a tumor-to-muscle ratio of 27.31 ± 7.03 at 2 h. The levels increased or remained steady for more than 72 h, and tumor uptake was significantly higher than 68Ga-NOTA-WL12, at 6.08 ± 0.62 at 2 h. Prolonged retention of 124I-WPMN makes it possible to conduct PET/MRI imaging over long periods and to perform various imaging techniques. A clear advantage of 124I-WPMN over 68Ga-NOTA-WL12 was observed for PDL1-targeted PET imaging after nanoparticle modification, supporting the utility of 124I-WPMN PET imaging as an effective diagnostic tool for optimizing PDL1-targeted therapies.
研究领域:
肿瘤学
·
医学影像
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Ping Cai,Sufan Tang,Li Xia,Yinwen Wang,Yang Liu,Yue Feng,Nan Liu,Yue Chen,Zhijun Zhou
Since prostate-specific membrane antigen (PSMA) is upregulated in nearly all stages of prostate cancer (PCa), PSMA can be considered a viable diagnostic biomarker and treatment target in PCa. In this study, we have developed five 68Ga-labeled PSMA-targeted tracers, 68Ga-Flu-1, 68Ga-Flu-2, 68Ga-9-Ant, 68Ga-1-Nal, and 68Ga-1-Noi, to investigate the effect of lipophilic bulky groups on the pharmacokinetics of PSMA inhibitors compared to 68Ga-PSMA-11 and then explore their in vitro and in vivo properties. 68Ga-labeled PSMA inhibitors were obtained in 88.53–99.98% radiochemical purity and at the highest specific activity of up to 20 MBq/μg. These compounds revealed a highly efficient uptake and internalization into LNCaP cells and increased over time. PET imaging and biodistribution studies were performed in mice bearing PSMA expressing LNCaP prostate cancer xenografts. All tracers enabled clear visualization of tumors in PET images with excellent tumor-to-background contrast. The biodistribution studies showed that all these radioligands were excreted mainly via the renal pathway. The in vivo biodistribution of 68Ga-Flu-1 revealed higher tumor uptake (40.11 ± 9.24 %ID/g at 2 h p.i.) compared to 68Ga-PSMA-11 (28.10 ± 5.96 %ID/g at 2 h p.i.). Both in vitro and in vivo experiments showed that chemical modification of the lysine fragment significantly impacts tumor-targeting and pharmacokinetic properties. Great potential to serve as new PET tracers for prostate cancer has been revealed with these radiotracers─68Ga-Flu-1 in particular.
研究领域:
医学影像
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肿瘤学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2021
·
IF 5.275
Gaochao Lv,Yinxing Miao,Yinfei Chen,Chunmei Lu,Xiuting Wang,Minhao Xie,Ling Qiu,Jianguo Lin
Programmed death ligand 1 (PD-L1) expression level is a reproducible biomarker for guiding stratification of patients to immunotherapy. However, the most widely used immunohistochemistry method is incompetent to fully understand the PD-L1 expression level in the whole body because of the highly complex PD-L1 expression in the tumor microenvironment. In this work, a novel small-molecular radiotracer [ 18 F]LG-1 based on the biphenyl active structure was developed to evaluate PD-L1 expression in tumors. [ 18 F]LG-1 was obtained by conjugating and radiolabeling with [ 18 F]FDG with high radiochemical purity (>98.0%) and high molar activity (37.2 ± 2.9 MBq/nmol). In vitro experimental results showed that [ 18 F]LG-1 could target PD-L1 in tumor cells and the cellular uptake in A375-hPD-L1 cells (PD-L1 + ) was clearly higher than that in A375 cells (PD-L1-). In vivo dynamic PET images of [ 18 F]LG-1 provided clear visualization of A375-hPD-L1 tumor with high tumor-to-background contrast, and the tumor uptake was determined to be 3.98 ± 0.21 %ID/g at 60 min, which was 2.6-fold higher than that of A375 tumor. These results suggested that [ 18 F]LG-1 had great potential as a promising PD-L1 radiotracer.
研究领域:
医学影像学
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肿瘤学
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核医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-10
·
IF 4.38
Chen Huanyu,Cai Ping,Feng Yue,Sun Zhanliang,Wang Yinwen,Chen Yue,Zhang Wei,Liu Nan,Zhou Zhijun
68 Ga-radiolabeled small molecules that specifically target prostate-specific membrane antigen (PSMA) have been extensively investigated, and some of these tracers have been used in the diagnosis of prostate cancer via 68 Ga-positron emission tomography ( 68 Ga-PET). Nevertheless, current 68 Ga-labeled radiotracers show only fair detection rates for metastatic prostate cancer lesions, especially those with lower levels of prostate specific antigen (PSA), which often occurs in the biochemical recurrence of prostate cancer. The goal of this study was to design and synthesize a new PSMA-targeted radiotracer, 68 Ga-SC691, with high affinity for prostate cancer cells and excellent pharmacokinetics. To this end, structural optimization was carried out on the bifunctional group, target motif, and linker while the high affinity targeting scaffold remained. To explore its potential in the clinic, a comparative study was further performed in vitro and in vivo between 68 Ga-SC691 and 68 Ga-PSMA-11, a clinically approved tracer for PSMA-positive prostate cancer. SC691 was radiolabeled to provide 68 Ga-SC691 in 99% radiolabeling yield under mild conditions. High uptake and a high internalization ratio into LNCaP cells were observed in in vitro studies. In vivo studies showed that 68 Ga-SC691 had favorable biodistribution properties and could specifically accumulate on PSMA-positive LNCaP xenografts visualized by micro-PET/CT. This radiotracer showed excellent PET imaging quality and comparable, if not higher, uptake in LNCaP xenografts than 68 Ga-PSMA-11.
研究领域:
医学影像学
·
肿瘤学
·
核医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED RADIATION AND ISOTOPES
·
2012
·
IF 1.172
Zhen-feng Liu,Guo-lin Wang,Meng-jie Dong,Qian Zhang,Jia-jun Li,Kui Zhao,Shu-ye Yang,Xiang-tong Lin
10-[ 11 C]methoxy-20(S)-camptothecin was synthesized automatically. The radiochemical yield was 30%–50% (all calculated at EOB, n =20) with [ 11 C]methyl triflate as a methylating agent. The radiochemical purity was greater than 96%, and the specific activity was 8.72±2.18 GBq/μmoL at EOS . Biodistribution showed that 10-[ 11 C]methoxy-20(S)-camptothecin is characterized by quick clearance from the blood and by significant uptake in the liver (5.72±1.92% ID/g at 15 min), intestines (2.43±0.38% ID/g at 15 min), and kidney (1.57±0.85% ID/g at 15 min). Micro-PET imaging clearly showed high radioactivity accumulation in liver, intestines and bladder, indicating that the primary modes of excretion of the radiotracer are through the hepatobiliary system and, to a lesser extent, through the renal system.
研究领域:
药理学
·
核医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）