JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2021
·Vol. 330
·期 3
·997-1005
·
IF 1.371
Yang Yuchuan,Wang Jing,Liu Wei,Deng Hao,Zhao Peng,Liao Wei,Wang Guanquan,Wei Hongyuan,Zhuo Liangang,Yang Xia
Death receptor 5 (DR5) is overexpressed in many tumors. Combination of the anti-DR5 antibody with radionuclides such as lutetium-177 ( 177 Lu) could enhance apoptosis and decrease the possibility of drug-induced resistance. In this study, a humanized anti-DR5 monoclonal antibody CTB006 was labeled with zirconium-89 ( 89 Zr) and 177 Lu to improve its efficiency for diagnosis and radiotherapy, respectively. The radiolabeled antibodies showed high tumor uptake in colon205 xenografts according to the results of micro-PET imaging and biodistribution. The 177 Lu-DOTA-CTB006 could inhibit tumor growth significantly.
研究领域:
肿瘤学
·
核医学
·
分子影像学
✓ 已验证
DOI
高影响因子
ChemistryOpen
·
2019
·Vol. 8
·期 4
·451-456
·
IF 2.205
Joo Hee Jang,Sang Jin Han,Jung Young Kim,Kwang Il Kim,Kyo Chul Lee,Chi Soo Kang
Graphical Conjugate for double duty : A new antibody-drug conjugate composed of paclitaxel (PTX), deferoxamine (DFO) and trastuzumab (DFO-trastuzumab-PTX) was prepared using simple conjugation chemistry. The new conjugate displayed instant complexation kinetics with 89 Zr and showed feasible cytotoxic effect and binding property on HER2-positive MDA-MB-231 breast cancer cell showing promising potential as a theranostic agent utilizing chemo-drug and positron emission tomography (PET). The preparation and in vitro evaluation of a theranostic conjugate composed of trastuzumab, paclitaxel (PTX), and deferoxamine (DFO)-chelated 89 Zr have been reported. These comounds have potential applications against HER2 receptor positive breast cancers. We conjugated DFO and PTX to trastuzumab by exploiting simple conjugation chemistry. The conjugate (DFO-trastuzumab-PTX) showed excellent radiolabeling efficiency with 89 Zr and the labeled conjugate had high in vitro stability in human serum. Furthermore, DFO-trastuzumab-PTX displayed comparable cytotoxicity with PTX and 89 Zr-DFO-trastuzumab-PTX exhibited HER2 receptor-mediated binding on HER2-positive MDA-MB-231 breast cancer cells. The results of our in vitro study indicate high potential of 89 Zr-DFO-trastuzumab-PTX to be utilized in the theranostic application against HER2-postive breast cancers.
研究领域:
肿瘤学
·
药理学
·
核医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Lixin Ding,Feng Wang,Zilei Wang,Yongxiang Pan,Teli Liu,Liansheng Cheng,Wenting Liu,Kuke Ding,Hua Zhu,Zhi Yang
Lymphocyte activation gene 3 (LAG-3) has attracted much attention as a potentially valuable immune checkpoint. Individual identification of LAG-3 expression at screening and during treatment could improve the successful implementation of anti-LAG-3 therapies. HuL13 is a human IgG1 monoclonal antibody that binds to the LAG-3 receptor in T cells. Here, we used [89Zr]Zr-labeled HuL13 to delineate LAG-3+ T-cell infiltration into tumors via positron emission tomography (PET) imaging. A549/LAG-3 cells, which stably express LAG-3, were generated by infection with lentivirus. The uptake of [89Zr]Zr-DFO-HuL13 in A549/LAG-3 cells was greater than that in the negative control (A549/NC) cells at each time point. The equilibrium dissociation constant (Kd) of [89Zr]Zr-DFO-HuL13 for the LAG-3 receptor was 8.22 nM. PET imaging revealed significant uptake in the tumor areas of A549/LAG-3 tumor-bearing mice from 24 h after injection (SUVmax = 2.43 ± 0.06 at 24 h). As a proof of concept, PET imaging of the [89Zr]Zr-DFO-HuL13 tracer was further investigated in an MC38 tumor-bearing humanized LAG-3 mouse model. PET imaging revealed that the [89Zr]Zr-DFO-HuL13 tracer specifically targets human LAG-3 expressed on tumor-infiltrating lymphocytes (TILs). In addition to the tumors, the spleen was also noticeably visible. Tumor uptake of the [89Zr]Zr-DFO-HuL13 tracer was lower than its uptake in the spleen, but high uptake in the spleen could be reduced by coinjection of unlabeled antibodies. Coinjection of unlabeled antibodies increases tracer activity in the blood pool, thereby improving tumor uptake. Dosimetry evaluation of the healthy mouse models revealed that the highest absorbed radiation dose was in the spleen, followed by the liver and heart wall. In summary, these studies demonstrate the feasibility of using the [89Zr]Zr-DFO-HuL13 tracer for the detection of LAG-3 expression on TILs. Further clinical evaluation of the [89Zr]Zr-DFO-HuL13 tracer may be of significant help in the stratification and management of patients suitable for anti-LAG-3 therapy.
研究领域:
癌症研究
·
免疫学
·
医学成像
·
核医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Xiaonan Wei,Chaoquan Lai,Xiaoyang Zhu,Aiyan Ji,Yeshan Qin,Shu Gao,Qiuyu Liu,Yonghao Li,Xuanyan Zhao,Hongyue Lou,Chunrong Qu,Zhen Cheng
Fibroblast activation protein (FAP) is an important target for the integrated diagnosis and treatment of tumors. However, FAP-targeted small molecule-based radiopharmaceuticals often face challenges such as low tumor uptake and short tumor retention, which hinder their biomedical and clinical applications. In this study, two radiolabeled FAP-targeted nanoprobes based on melanin nanoparticles (MNPs) were designed and developed in order to evaluate their potential for FAP-targeted theranostics. The excellent metal ion complexing property of melanin allowed 89Zr to be efficiently labeled on the MNP platform. After PEGylated MNPs were modified with small molecules FAPI-04 and GPFAPI-04 and radiolabeled with 89Zr to obtain [89Zr]Zr–F-MNPs and [89Zr]Zr-GPF-MNPs, these two nanoprobes achieved active targeting through FAPI ligands. The radiochemical purity of 89Zr-labeled nanoprobes remained above 90% in fetal bovine serum (FBS) solution in 72 h. In vitro experiments showed that both [89Zr]Zr–F-MNPs and [89Zr]Zr-GPF-MNPs were taken up by FAP high-expressing U87MG cells (2.58 ± 0.07% vs 3.00 ± 0.10% for 2 h; 2.93 ± 0.08% vs 3.62 ± 0.04% for 4 h). For the in vivo study, at 48 h postinjection (p.i.) of the nanoprobe, the U87MG tumor uptake of [89Zr]Zr–F-MNPs and [89Zr]Zr-GPF-MNPs reached 4.83 ± 0.50% ID/g and 5.13 ± 0.38% ID/g, respectively. Blocking experiments further confirmed the FAP-dependent targeting ability. Neither of the two nanoprobes elicited observable adverse effects in vivo. In conclusion, the FAPI-MNPs-based nanoprobe platform, which integrates active targeting and passive accumulation, improves tumor uptake and retention time of FAP-targeted radioligands with excellent biosafety. This study offers a new strategy and platform for the development of FAP-targeted diagnostic and therapeutic probes with promising clinical translation potential.
✓ 已验证
产品关联
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
·
细胞生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2021
·
IF 4.774
Yawen Zeng,Jinling Xiao,Yiyang Cong,Jia Liu,Yiming He,Brian D. Ross,Haixing Xu,Yihua Yin,Hao Hong,Wenjin Xu
Nanoscale metal–organic frameworks (nMOFs) are a unique type of hybrid materials, which are broadly applicable as cargo delivery systems. However, the relatively low material stability and insufficient cancer cell interacting capacity have limited nMOFs’ applications in cancer theranostics. Herein, a zirconium-based nMOF UiO-66-N3 was synthesized, and its surface was covalently functionalized with alkyne-containing polyethylene glycol (PEG) via the azide–alkyne click chemistry. After that, F3 peptide was attached for targeting of cancer cells (the material was denoted as UiO-66-PEG-F3). Doxorubicin (DOX) served as a therapeutic drug and a fluorescent label in this study, and it was transported into UiO-66-PEG conjugates with sufficient drug loading efficiency. pH-responsive release of DOX from UiO-66 conjugates was witnessed. The structural integrity of UiO-66-N3 was maintained post the surface modification process. Flow cytometry and confocal fluorescence microscopy revealed that DOX/UiO-66-PEG-F3 had stronger accumulation in MDA-MB-231 cells (nucleolin+) compared with DOX/UiO-66-PEG. In order to track the pharmacokinetic behavior (organ distribution profile) in vivo, the positron-emitting zirconium-89 (89Zr) was incorporated into UiO-66-N3. Similar PEGylation and F3 peptide conjugation resulted in the formation of 89Zr-UiO-66-PEG-F3. Serial positron emission tomography (PET) imaging demonstrated that the preferential accumulation of 89Zr-UiO-66-PEG-F3 in MDA-MB-231 tumors, and their liver clearance was faster than PEGylated UiO-66 using noncovalent methods. Thus, the PEGylated nMOFs using covalent strategies may find broad application in future cancer theranostics.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Huihui Liu,Qing Wang,Jingru Guo,Kai Feng,Yiling Ruan,Zhihao Zhang,Xin Ji,Jigang Wang,Tao Zhang,Xiaolian Sun
Cerenkov radiation induced photodynamic therapy (CR-PDT) can tackle the tissue penetration limitation of traditional PDT. However, co-delivery of radionuclides and photosensitizer may cause continuous phototoxicity in normal tissues during the circulation. 5-aminolevulinic acid (ALA) which can intracellularly transform into photosensitive protoporphyrin IX (PpIX) is a cancer-selective photosensitizer with negligible side effect. However, the hydrophilic nature of ALA and the further conversion of PpIX to photoinactive Heme severely hinder the therapeutic benefits of ALA-based PDT. Herein, we developed an 89 Zr-labeled, pH responsive ALA and artemisinin (ART) co-loaded liposome ( 89 Zr-ALA-Liposome-ART) for highly selective cancer therapy. 89 Zr can serve as the internal excitation source to self-activate PpIX for CR-PDT, and the photoinactive Heme can activate the chemotherapeutic effect of ART. The 89 Zr-ALA-Liposome-ART exhibited excellent tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c mice via CR-PDT and chemotherapy. Combined with anti-PD-L1, the 89 Zr-ALA-Liposome-ART elicited strong antitumor immunity to against tumor recurrence.
研究领域:
药学
·
放射肿瘤学
·
纳米技术
·
免疫疗法
✓ 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）