ACS Omega
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2026
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IF 5.2
Huanyu Chen,Yuduo Wan,Wanlu Feng,Changjiang Wang,Yang Wang,Yue Chen,Takron Chantadee,Zibo Li,Li Wang
Nectin-4, a cell adhesion molecule frequently overexpressed in non-small cell lung cancer (NSCLC), has emerged as a promising target for theranostic applications due to its involvement in tumor progression and association with poor prognosis. This study aimed to develop radiolabeled agents based on bicyclic peptides for both imaging and targeted therapy for Nectin-4 positive tumors. We designed and synthesized 68Ga-labeled probes ([68Ga]Ga-3 and [68Ga]Ga-5) for PET imaging and 177Lu-labeled agents ([177Lu]Lu-6) for targeted radionuclide therapy. Radiochemical yields and purity were optimized, and the agents were evaluated for cellular uptake, internalization, and biodistribution in Nectin-4-expressing cell lines (H1975, ABC-1, HEK293nectin4) and xenograft models. Target specificity was confirmed through blocking studies with the Nectin-4 specific inhibitor peptide N188. The 68Ga-labeled probes exhibited high radiochemical yields (78–81%) and purity (>95%), with specific uptake observed in Nectin-4-positive cells (e.g., 69.20 ± 2.31%ID/106 cells for [68Ga]Ga-3 at 120 min) and tumors. Blocking studies resulted in significant reductions in uptake, with 39-fold and 22-fold decreases for [68Ga]Ga-3 and [68Ga]Ga-5, respectively, confirming Nectin-4 specificity. [177Lu]Lu-6 showed superior tumor retention (13% uptake) and internalization (3.5%) compared to [177Lu]Lu-FAP-2286/N188, with sustained tumor growth suppression in xenograft models. PET/SPECT imaging revealed high tumor-to-background ratios and favorable pharmacokinetics, highlighting the potential of these agents for clinical application.
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DOI
PubMed
高影响因子
Frontiers in Medicine
·
2023
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IF 3.9
Ding Ying,Liu Yu,Zhang Li,Deng Yinqian,Chen Huanyu,Lan Xiaoli,Jiang Dawei,Cao Wei
Background: Early detection of kidney diseases can be challenging as conventional methods such as blood tests or imaging techniques (computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography) may be insufficient to assess renal function. A single-photon emission CT (SPECT) renal scan provides a means of measuring glomerular filtration rates (GFRs), but its diagnostic accuracy is limited due to its planar imaging modality and semi-quantification property. In this study, we aimed to improve the accuracy of GFR measurement by preparing a positron emission tonometry (PET) tracer 68Ga-Ethylenediaminetetraacetic acid (68Ga-EDTA) and comprehensively evaluating its performance in healthy mice and murine models of renal dysfunction.Methods: Dynamic PET scans were performed in healthy C57BL/6 mice and in models of renal injury, including acute kidney injury (AKI) and unilateral ureter obstruction (UUO) using 68Ga-EDTA. In a 30-min dynamic scan, PET images and time-activity curves (TACs) were acquired. Renal function and GFR values were measured using renograms and validated through serum renal function parameters, biodistribution results, and pathological staining.Results: 68Ga-EDTA dynamic PET imaging quantitatively captured the tracer elimination process. The calculated GFR values were 0.25 ± 0.02 ml/min in healthy mice, 0.01 ± 0.00 ml/min in AKI mice, and 0.25 ± 0.04, 0.29 ± 0.03 and 0.24 ± 0.01 ml/min in UUO mice, respectively. Furthermore, 68Ga-EDTA dynamic PET imaging and GFRPET were able to differentiate mild renal impairment before serum parameters indicated any changes.Conclusions: Our findings demonstrate that 68Ga-EDTA dynamic PET provides a reliable and precise means of evaluating renal function in two murine models of renal injury. These results hold promise for the widespread clinical application of 68Ga-EDTA dynamic PET in the near future.
研究领域:
医学影像学
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核医学
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肾脏生理学
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实验病理学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2026
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IF 4.9
Jie Li,Yuhui Luo,Chengyu Luo,Zixin Yang,Fei Luo,Huajian Gu,Fei Chen,Zongxi He,Suping Li
Abstract Carbonic anhydrase IX (CA IX) is a key biomarker for tumor hypoxia and a promising target for molecular imaging. In this study, we developed [68Ga]Ga-DOTA-L3, a novel small-molecule CA IX-targeted PET tracer. The radiolabeling was optimized to consistently achieve a radiochemical purity of >98% (10 μg precursor, 90 °C, pH 4.5, 10 min), with excellent stability in saline and FBS up to 240 min. In vivo studies demonstrated rapid blood clearance and predominant renal excretion. Surface plasmon resonance analysis demonstrated high-affinity binding of the DOTA-L3 precursor toward CA IX (Kd = 7.60 ± 0.37 nM) with highest affinity observed for CA IX among the tested isoforms. MicroPET/CT imaging (30−240 min p.i.) showed robust tumor accumulation in OSRC-2 (SUVmean = 1.47 ± 0.21) and HT-29 (SUVmean = 1.03 ± 0.12) xenografts, while minimal uptake was observed in CA IX-low FTC-238 tumors (SUVmean = 0.21 ± 0.05) at 60 min p.i. PET-derived tumor uptake showed a strong linear correlation with CA IX expression levels (R2 = 0.976, P < 0.001) across the three tumor models. High tumor-to-muscle and tumor-to-blood ratios further confirm favorable imaging contrast (T/M = 27.53 ± 1.89 and T/B = 24.61 ± 2.35 at 240 min p.i. for OSRC-2 model). These results support [68Ga]Ga-DOTA-L3 as a promising candidate for non-invasive assessment of CA IX-associated hypoxia and as a scaffold for future theranostic development.
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DOI
高影响因子
EJNMMI Research
·
2024
·Vol. 14
·期 1
·1-13
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IF 3.1
Liu Yang,Xia Li,Li Haiyang,Cai Ping,Tang Sufan,Feng Yue,Liu Guangfu,Chen Yue,Liu Nan,Zhang Wei,Zhou Zhijun
Background Prostate cancer is the second most frequent cancer and the fifth leading cause of cancer-related deaths in men. Prostate-specific membrane antigen (PSMA) as a target has gained increasing attention. This research aims to investigate and understand how altering size of PEG impacts the in vitro and in vivo behavior and performance of PSMA inhibitors, with a specific focus on their pharmacokinetic characteristics and targeting properties. Results Two 68 Ga-labeled PSMA-targeted radiotracers were developed, namely [ 68 Ga]Ga-PP4-WD and [ 68 Ga]Ga-PP8-WD, with varying sizes of polyethylene glycol (PEG). [ 68 Ga]Ga-PP4-WD and [ 68 Ga]Ga-PP8-WD had excellent affinity for PSMA with IC50 being 8.06 ± 0.91, 6.13 ± 0.79 nM, respectively. Both tracers enabled clear visualization of LNCaP tumors in PET images with excellent tumor-to-background contrast. They also revealed highly efficient uptake and internalization into LNCaP cells, increasing over time. The biodistribution studies demonstrated that both radioligands exhibited significant and specific uptake into LNCaP tumors. Furthermore, they were rapidly cleared through the renal pathway, as evidenced by [ 68 Ga]Ga-PP4-WD and [ 68 Ga]Ga-PP8-WD showing a tenfold and a fivefold less in renal uptake, respectively, compared to [ 68 Ga]Ga-Flu-1 in 30 min. Both in vitro and in vivo experiments demonstrated that PEG size significantly impacted tumor-targeting and pharmacokinetic properties. Conclusions These radiotracers have demonstrated their effectiveness in significantly reducing kidney uptake while maintaining the absorbed dose in tumors. Both radiotracers exhibited strong binding and internalization characteristics in vitro, displayed high specificity and affinity for PSMA in vivo .
研究领域:
医学肿瘤学
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分子成像
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药理学
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生物化学
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核医学
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DOI
高影响因子
MOLECULAR PHARMACEUTICS
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2023
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IF 4.9
Pei Wang,Shuailiang Wang,Futao Liu,Ya’nan Ren,Qian Guo,Qian Zhang,XingGuo Hou,Yuan Yao,Hua Zhu,Zhi Yang
Prostate-specific membrane antigen (PSMA) is a prostate cancer target that plays a crucial role in prostate cancer diagnosis and therapy. Herein, a novel dual-targeted imaging probe, [68Ga]Ga-FAPI-PSMA, was prepared by radiolabeling conjugated DOTA-FAPI-PSMA with the short half-life radionuclide gallium-68 (68Ga), which is dedicated to prostate cancer diagnostic imaging. In vitro, [68Ga]Ga-FAPI-PSMA had higher affinity for the PSMA and FAP high-expressing cell lines 22Rv1 and U87 MG with IC50 values of 4.73 and 2.10 nM, respectively, than in the corresponding negative expression cell lines PC3 and A549, and significant differences in cell uptake were also observed. In vivo, [68Ga]Ga-FAPI-PSMA was rapidly cleared from the body, and the estimated radiation dose was relatively low compared with several other FAPI probes. In 22Rv1 and U87 MG tumor xenografts, [68Ga]Ga-FAPI-PSMA rapidly accumulated in tumors after administration, and the best images can be obtained at 1 h postinjection. In conclusion, the dual-targeted probe [68Ga]Ga-FAPI-PSMA was successfully prepared for in vivo prostate cancer PET/CT imaging.
研究领域:
放射学
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肿瘤学
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分子影像
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核医学
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2022
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IF 14.026
Yinfei Chen,Shiyu Zhu,Jiayu Fu,Jianguo Lin,Yan Sun,Gaochao Lv,Minhao Xie,Tao Xu,Ling Qiu
Despite advances in immunotherapy for the treatment of cancers, not all patients can benefit from programmed cell death ligand 1 (PD-L1) immune checkpoint blockade therapy. Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level; hence, accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects. Therefore, based on the high affinity antibody Nb109, a new site-specifically radiolabeled tracer, 68 Ga-NODA-cysteine, aspartic acid, and valine (CDV)-Nb109, was designed and synthesized to accurately monitor PD-L1 expression. The tracer 68 Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95% and radiochemical purity of 97%. It showed high affinity for PD-L1 with a dissociation constant of 12.34 ± 1.65 nM. Both the cell uptake assay and positron emission tomography (PET) imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells. Meanwhile, dynamic PET imaging of a NCI-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression, allowing timely interventional immunotherapy. In conclusion, this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
研究领域:
肿瘤学
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免疫学
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医学影像学
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药学
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6.8
Xin Xiang,Chuning Dong,Lianbo Zhou,Jun Liu,Zachary M. Rabinowitz,Yuzhao Zhang,Honghui Guo,Feng He,Xingdou Chen,Yunhua Wang,Lina Cui,Xiaowei Ma
Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated β-galactosidase (SA-β-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]Ga-BGal displayed high sensitivity and specificity for β-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the β-Gal concentration and reaction time. In PET imaging, high β-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [68Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.
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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放射学
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药学
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产品关联
DOI
PubMed
高影响因子
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