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
✓ 已验证
DOI
PubMed
高影响因子
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2023
·
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
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
✓ 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）