Scientific Reports
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2021
·Vol. 11
·期 1
·1-10
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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
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肿瘤学
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核医学
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2024
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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
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2023
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IF 4.9
Haiyan Hong,Zhihao Zha,Ruiyue Zhao,Yang Luo,Wenbin Jin,Linlin Li,Ran Wang,Li Yan,Hui Wang,Karl Ploessl,Jinping Qiao,Lin Zhu,Hank F. Kung
Fibroblast activation protein (FAP) is selectively expressed in tumors and highly important for maintaining the microenvironment in malignant tumors. Radioisotope-labeled FAP inhibitors (FAPIs) were proven to be useful for diagnosis and radionuclide therapy of cancer and are under active clinical investigations. Ga-HBED complex displays a higher in vivo stability constant (log KGaL: 38.5), compared to that of Ga-DOTA (log KGaL: 21.3). Such advantage in stability constant suggests that it may be useful for development of alternative FAPI imaging agents. In this study, previously reported [68Ga]Ga-DOTA-FAPI-02 and -04 were converted to the corresponding [68Ga]Ga-HBED-CC-FAPI-02 and -04 derivatives ([68Ga]Ga-4, [68Ga]Ga-5, [68Ga]Ga-6, and [68Ga]Ga-7). It was found that substituting the DOTA chelating group with HBED-CC led to several unique and desirable tumor-targeting properties: (1) robust, fast, and high yield labeling─readily adaptable to a kit formulation; (2) high stabilities in vitro; (3) excellent FAP binding affinities (IC50 ranging between 4 and 7 nM) and improved cell uptake and retention (in HT1080 (FAP+) cells); and (4) excellent selective in vivo tumor uptake in nude mice bearing U87MG tumor. It appeared that Ga(III) chelation with HBED-CC improved the in vivo kinetics favoring higher tumor uptake and retention compared to the corresponding Ga-DOTA complex. Out of the four tested ligands the new [68Ga]Ga-HBED-CC-FAPI dimer, [68Ga]Ga-6, displayed the best tumor localization properties, and further studies are warranted to demonstrate that it is an alternative FAP imaging agent for cancer patients.
研究领域:
医学影像学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
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2023
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IF 6.7
Chen Qin,Fu Xiaomin,Cai Huawei,Fu Shengxiang,Cai Zhongyuan,Li Mufeng,Wu Xiaoai,Tian Rong,Ai Hua
Precise diagnosis of lymph node metastasis is important for therapeutic regimen planning, prognosis analysis and probably better outcomes for cancer patients. In this work, 68Ga-labeled amphiphilic alternating copolymers nanoparticles with different rigid ligands were synthesized as positron emission tomography (PET) probes for lymph node metastasis imaging. The labeling efficiency and stability of nanoparticles was improved with increased rigidity of coordination unit. PU(68Ga-L-MDI-PEG) nanoparticles (PU(68Ga-L-MDI-PEG) NPs) with the strongest rigidity of coordination unit exhibited the lowest critical micelle concentration, the best 68Ga labeling efficiency and stability. During in vivo lymph node metastasis imaging, PU(68Ga-L-MDI-PEG) NPs led to different accumulations in normal lymph nodes (N-LN) and tumor metastasized sentinel lymph nodes (T-SLN), which resulted in different PET signal presentation, making it feasible to differentiate N-LN from T-SLN. In comparison, small molecule probe 68GaL had poor lymph node accumulation, not only making it difficult to find lymph nodes on PET/computed tomography scan, but also tough to distinguish N-LN from metastatic ones. Overall, this work provides a reference for design of 68Ga labeled polymeric nanoparticles with high chelation efficiency and stability, as sensitive PET probes for lymph node imaging.
研究领域:
医学影像学
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肿瘤学
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核医学
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产品关联
DOI
PubMed
高影响因子
APPLIED RADIATION AND ISOTOPES
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2025
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IF 1.8
Tao Gao,Xiang Gong,Jiali Liu,Sheng Hu,Wei Yu,Yuhong Liu,Jiwei Liang
A method for regulating the rutile and anatase ratio of TiO 2 products by adding tartaric acid is reported. By this method, TiO 2 with a specific anatase/rutile ratio exhibited excellent selective adsorption performance of 68 Ge and 68 Ga. Experiment shows that Tartaric acid assist synthesized TiO 2 enabled strong 68 Ge adsorption but negligible adsorption of 68 Ga. Meanwhile, the TiO 2 adsorption exhibited significant acid resistance, with minimal Ti 4+ leaching. In addition, the 68 Ga elution efficiency and 68 Ge breakthrough of radioactivity experiments demonstrated that synthesized TiO 2 achieved an initial 68 Ga elution efficiency of 75%, which remained about 65% after 200 elution cycles. Furthermore, over the four-month observation period, the 68 Ge breakthrough of the TiO 2 adsorbent did not exhibit a significant increase, remaining below 1×10 -5 . Generally, the synthesized TiO 2 adsorbent exhibits potential as a 68 Ge/ 68 Ga generator column adsorbent with outstanding acid-resistant, radiation-resistant, efficient 68 Ga elution and low 68 Ge breakthrough for long-term.
研究领域:
材料科学
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核化学
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吸附技术
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放射性药物
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
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2024
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IF 8.6
Song Yangmeihui,Qin Chunxia,Chen Yixiong,Ruan Weiwei,Gai Yongkang,Song Wenyu,Gao Yu,Hu Wenzhu,Qiao Pengxin,Song Xiangming,Lv Xiaoying,Zheng Danzha,Chu Huikuan,Jiang Dawei,Yang Ling,Lan Xiaoli
Purpose The reversibility of early liver fibrosis highlights the need for improved early detection and monitoring techniques. Fibroblast activation protein (FAP) is a promising theranostics target significantly upregulated during fibrosis. This preclinical and preliminary clinical study investigated a FAP-targeted probe, gallium-68-labeled FAP inhibitor 04 ([ 68 Ga]Ga-DOTA-FAPI-04), for its capability to visualize liver fibrosis. Methods The preclinical study employed [ 68 Ga]Ga-DOTA-FAPI-04 micro-positron emission tomography (PET)/computed tomography (CT) on carbon tetrachloride-induced mice model (n = 34) and olive oil-treated control group (n = 26), followed by validation of the probe's biodistribution. Hepatic uptake was correlated with fibrosis and inflammation levels, quantified through histology and serum assays. FAP and α-smooth muscle actin expression were determined by immunohistochemistry, as well as immunofluorescence. The subsequent clinical trial enrolled 26 patients with suspected or confirmed liver fibrosis to undergo [ 68 Ga]Ga-DOTA-FAPI-04 PET/magnetic resonance imaging or PET/CT. Key endpoints included correlating [ 68 Ga]Ga-DOTA-FAPI-04 uptake with histological inflammation grades and fibrosis stages, and evaluating its diagnostic and differential efficacy compared to established serum markers and liver stiffness measurement (LSM). Results [ 68 Ga]Ga-DOTA-FAPI-04 mean uptake in mice livers was notably higher than in control mice, increasing from week 6 [0.70 ± 0.11 percentage injected dose per cubic centimeter (%ID/cc)], peaking at week 10 (0.97 ± 0.15%ID/cc) and slightly reducing at week 12 (0.89 ± 0.28%ID/cc). The hepatic biodistribution and FAP expression showed a consistent trend. In the patient cohort, hepatic [ 68 Ga]Ga-DOTA-FAPI-04 uptake presented moderate correlations with inflammation grades (r = 0.517 to 0.584, all P < 0.05) and fibrosis stages (r = 0.653 to 0.698, all P < 0.01). The average SUVmax to background ratio in the liver showed superior discriminative ability, especially between stage 0 and stage 1, outperforming LSM (area under curve 0.984 vs. 0.865). Conclusion [ 68 Ga]Ga-DOTA-FAPI-04 PET shows significant potential for non-invasive visualization and dynamic monitoring of liver fibrosis in both preclinical experiment and preliminary clinical trial, especially outperforming other common clinical indicators in the early stage. Trial registration NCT04605939. Registered October 25, 2020, https://clinicaltrials.gov/study/NCT04605939
研究领域:
医学影像学
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肝脏病学
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分子影像学
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产品关联
DOI
PubMed
高影响因子
Contrast Media & Molecular Imaging
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2019
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IF 1.984
Zi Wang,Liang Cai,Tingting Xu,Dan Tang,Lin Liu,Yue Chen
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic, symmetrical, and erosive synovitis. RA is one of the most common disabling diseases in the clinic. The main clinical intervention strategies are early diagnosis and early treatment. This study aims to predict the diagnostic value of 68Ga-citrate and 18F-FDG PET/CT in RA by comparing and analyzing the value of 68Ga-citrate and 18F-FDG PET/CT for diagnosing type II collagen-induced arthritis (CIA) in rats. Some CIA models were established. Normal rats were selected as the control group, and 23 days and 40 days were selected as the early and late time points of arthritis, respectively. The semiquantitative analysis of CIA rats was carried out with 68Ga-citrate PET/CT and 18F-FDG PET/CT, and the ratio of the maximum standardized uptake (SUVmax) values in the regions of interest (ROIs) of the hind foot ankle joint and thigh muscle was calculated and statistically analyzed. The distribution of CIA rats in vivo at the 68Ga-citrate 90 min time point was studied, and the ankle tissues were evaluated with hematoxylin and eosin (HE) staining. 68Ga-citrate PET/CT is obviously superior to 18F-FDG PET/CT for CIA imaging, and the statistical results show that the difference between the two examination methods is statistically significant (). The uptake of these two radiopharmaceuticals showed the same trend in arthritis rats with different scores. The distribution of 68Ga-citrate at 90 min is consistent with the trend shown by 68Ga-citrate PET/CT. 68Ga-citrate PET/CT can reflect the inflammatory activity of affected joints in CIA rats earlier and more sensitively than 18F-FDG PET/CT, and this imaging advantage continues until the later stage of inflammation. Therefore, 68Ga-citrate PET/CT is worthy of further promotion and application in the clinical diagnosis of RA.
研究领域:
医学影像学
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风湿病学
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DOI
PubMed
高影响因子
Frontiers in Oncology
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2022
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IF 5.738
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.
研究领域:
肿瘤学
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医学影像学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2021
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IF 9.229
Rui Zou,Yifan Gao,Yong Zhang,Ju Jiao,Ka-Leung Wong,Jing Wang
Featured with a zero-autofluorescence background, superior signal-to-noise ratio, high sensitivity, and deep penetration ability, near-infrared persistent luminescence nanoparticle (NIR-PLNP)-based multimodal nanoprobes show great potential for full-scale noninvasive cancer diagnosis. However, direct synthesis of NIR-PLNP-based multimodal nanoprobes with high drug loading capacity to meet growing cancer theranostic demands remains a challenge. In this work, multifunctional hybrid mesoporous nanoparticles (HMNPs) that integrate NIR-PLNPs (Ga2O3:Cr3+, Nd3+), magnetic nanoparticles (Gd2O3), and radionuclides (68Ga) are designed and constructed via a large-pore (mesoporous silica nanoparticle) MSN-templated strategy. The ingenious composition design endows HMNPs with rechargeable NIR-PL, superior longitudinal relaxivity, and excellent radioactivity, making these versatile nanoparticles available for long-term in vivo NIR-PL imaging, magnetic resonance imaging (MRI), and positron emission tomography (PET) imaging. More importantly, the application of large-pore MSN templates maintains the mesoporous structure of HMNPs, promising excellent drug loading capacity of these nanoparticles. As a proof-of-concept, HMNPs loaded with a high dose of DOX (chemotherapy agent) and Si-Pc (photosensitizer) are rationally designed for chemotherapy and NIR-PL-sensitized photodynamic therapy (PDT), respectively. Studies with mice tumor models demonstrate that the DOX/Si-Pc-loaded HMNPs possess excellent cancer cell killing ability and an outstanding tumor suppression effect without systemic toxicity. This work shows the great potential of HMNPs as an “all-in-one” nanotheranostic tool for multimodal NIR-PL/MR/PET imaging-guided chemotherapy and NIR-PL-sensitized photodynamic cancer therapy and provides an innovative paradigm for the development of NIR-PLNP-based nanoplatforms in cancer theranostic.
研究领域:
癌症诊疗学
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材料科学
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纳米医学
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医学成像
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放射学
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产品关联
DOI
PubMed
高影响因子
Research
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2022
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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
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药理学
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DOI
高影响因子
MOLECULAR PHARMACEUTICS
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2025
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IF 4.5
Nianting Ju,Boyu Tan,Hongyue Lou,Ying Zhang,Kun Qian,Chunrong Qu,Quanyong Luo,Zhen Cheng
As an important tumor-associated carbohydrate antigen, the Thomsen–Friedenreich (T or TF) antigen has become an attractive target for tumor diagnosis and treatment. However, there has been very limited success in developing peptide- and small-molecule-based radiopharmaceuticals for this important target. Currently, only 64Cu-NO2A-TFpep has been reported as a radiolabeled peptide targeting the TF antigen, and it shows a low tumor-to-liver ratio due to 64Cu retention in the liver. In this study, a novel PET probe targeting the TF antigen (DOTA-TFpep) was synthesized using 2,2′,2″,2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) chelator for increasing the hydrophilic property and for radiolabeling with different radionuclides. DOTA-TFpep was then radiolabeled with 68Ga for positron emission tomography (PET) imaging of breast tumors expressing the TF antigen. 68Ga-DOTA-TFpep was confirmed by radio-HPLC with a purity greater than 98% and high stability in PBS. Immunofluorescence analysis confirmed the TF antigen expression of 4T1 and K1 cell lines. Cell uptake studies confirmed its targeting specificity. Further in vivo biodistribution studies in high (4T1) and low (K1) TF antigen-expression xenograft models demonstrated the favorable pharmacokinetics property of the probe. PET imaging and biodistribution showed that 68Ga-DOTA-TFpep exhibited specific tumor uptake. Moreover, compared with the widely studied 64Cu-NO2A-TFpep, 68Ga-DOTA-TFpep showed lower liver uptake and a higher tumor-to-liver ratio (1.31 ± 0.20 for 64Cu-NO2A-TFpep and 0.48 ± 0.15 for 68Ga-DOTA-TFpep at 120 min after injection). In summary, this study demonstrates the synthesis and evaluation of the TF antigen-targeting probe 68Ga-DOTA-TFpep. It shows favorable in vivo tumor imaging properties, highlighting it as a promising molecular probe targeting the TF antigen.
✓ 已验证
DOI
PubMed
高影响因子
American Journal of Nuclear Medicine and Molecular Imaging
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2022
·
IF 0
Ying Ding,Du Zhang,Min Wang,Li Zhang,Yu Liu,Yinqian Deng,Dawei Jiang,Yuqing Liu,Wei Cao
Positron emission tomography (PET) can accurately locate and quantify radioactivity over traditional single photon emission computed tomography (SPECT), encouraging its application in kidney function evaluation and glomerular filtration rate (GFR) measurement. 68 Ga-ethylenediamine-tetraacetic acid ( 68 Ga-EDTA) is a novel PET tracer for renal scan but a mature GFR calculation method still pending establishment. Herein, we aim to investigate the imaging performance of 68 Ga-EDTA dynamic PET in healthy C57BL/6 mice, establish quantitative methods to calculate GFR, and evaluate its feasibility in mice with kidney dysfunction. Dynamic PET of 68 Ga-EDTA successfully visualized the whole process of tracer elimination. GFR values were measured by the integral method (253.80±40.11 μL/min) and the Patlak Plot method (22.69±9.75 μL/min), while blood clearance rate of the tracer was found at 787.46±70.86 μL/min. The PET-based GFR values correlate well with the GFR blood (R 2 =0.7468, R 2 =0.8793). The Integral method provides better accuracy than Patlak Plot method. Further application of GFR measurement in kidney-diseased mice proves better performance of the Integral method for defining split renal function.
研究领域:
医学成像
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核医学
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肾脏生理学
✓ 已验证
DOI
PubMed
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