JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2024
·
IF 1.5
Xu Xiang,Mao Yiyin,Zhou Peng,Wu Yujing,Liu Yaling,Wang Hongyong,Lu Chunxiong,Zou Pei
In this study, a 99m Tc-labeled small molecule imaging probe [ 99m Tc]Tc-PG3C-CBM for PD-L1 imaging was designed. It showed a radiochemical yield of > 97% and good in vitro stability. Uptake in A375-hPD-L1 cells (17.07 ± 1.40%) was 4.5 times higher than in A375 cells (3.81 ± 0.19%). The probe demonstrated moderate PD-L1 affinity (K D : 11.6 ± 2.57 nM; IC 50 : 59.2 ± 2.40 nM). Additionally, SPECT/CT imaging and biodistribution results indicated that [ 99m Tc]Tc-PG3C-CBM was mainly metabolized by the liver and showed some accumulation at the tumor site. These results suggest that [ 99m Tc]Tc-PG3C-CBM could potentially target PD-L1 at tumor sites.
研究领域:
核医学
·
分子影像学
·
肿瘤学
✓ 已验证
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Huan Ma,Feize Li,Guohua Shen,Huawei Cai,Weihao Liu,Tu Lan,Yuanyou Yang,Jijun Yang,Jiali Liao,Ning Liu
As an excellent target for cancer theranostics, fibroblast activation protein (FAP) has become an attractive focus in cancer research. A class of FAP inhibitors (FAPIs) with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold were developed, which displayed nanomolar affinity and high selectivity. Compared with 90Y, 177Lu, 225Ac, and 188Re, 211At seems to be more favored as a therapeutic candidate for FAPI tracers which have fast washout and short retention in tumor sites. Thus, the current study reported the synthesis of two FAPI precursors for 211At and 131I labeling and the preliminary evaluation of 131I-labeled FAPI analogues for cancer theranostics. FAPI variants with stannyl precursors were successfully synthesized and labeled with 131I using a radioiododestannylation reaction. Two radioactive tracers were obtained with high radiochemical purity over 99% and good radiochemical yields of 58.2 ± 1.78 and 59.5 ± 4.44% for 131I-FAPI-02 and 131I-FAPI-04, respectively. Both tracers showed high specific binding to U87MG cells in comparison with little binding to MCF-7 cells. Compared to 131I-FAPI-02, 131I-FAPI-04 exhibited higher affinity, more intracellular uptake, and longer retention time in vitro. Biodistribution studies revealed that both tracers were mainly excreted through the kidneys as well as the hepatobiliary pathway due to their high lipophilicity. In addition, higher accumulation, longer dwell time, and increased tumor-to-organ ratios were achieved by 131I-FAPI-04, which was clearly demonstrated by SPECT/CT imaging. Furthermore, intratumor injection of 131I-FAPI-04 significantly suppressed the tumor growth in U87MG xenograft mice without significant toxicity observed. The above results implied that FAP-targeted alpha endoradiotherapy (specific to 211At) should be used to treat tumors in the near future, considering the chemical similarity between iodine and astatine can ensure the labeling of the latter onto the designed FAPIs.
研究领域:
肿瘤学
·
核医学
·
分子影像学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2018
·
IF 0
Caixia Sun,Yifan Xu,Lijuan Deng,Hao Zhang,Qiao Sun,Chongjun Zhao,Zhen Li
Black phosphorus (BP) nanostructures have been receiving enormous attention in diverse bioapplications owing to their unique physicochemical properties. However, it is still challenging to investigate their blood circulation, biodistribution, and pharmacokinetics after administration due to the difficulty in quantifying them. Here, we report the quantification of blood circulation, biodistribution, and pharmacokinetics of dextran-modified BP nanoparticles (i.e., BP-DEX NPs) in balb/c mice through the highly sensitive noninvasive photoacoustic (PA) imaging and single-emission computed tomography/computed tomography (SPECT/CT) imaging. We first prepare water-soluble and biocompatible small BP-DEX NPs and label them with radioisotopes 99mTc. We then quantify their half-lives of distribution and elimination phases to be 0.2 and 9.5 h by counting the γ-emissions in the blood of mice administrated with BP-DEX NPs. We also show the dynamic variation of BP-DEX NPs in the tumor, liver, spleen, and kidney through in vivo PA imaging and illustrate the accumulation of nanoparticles in major organs by SPECT/CT imaging, which follows an order of spleen > liver > lung > kidney. Our work demonstrates the renal clearance and hepatobiliary excretion of BP-DEX NPs, which could be potentially translated for clinical in vivo imaging and therapy of cancer.
研究领域:
生物医学工程
·
纳米医学
·
药物递送
✓ 已验证
产品关联
DOI
PubMed
BIOCONJUGATE CHEMISTRY
·
2016
·
IF 4.5
Jianbo Li,Dawei Jiang,Baoliang Bao,Yulin He,Lei Liu,Xuemei Wang
Self-assembled DNA nanostructures, as a new type of nanocarriers, have shown great potential in molecular imaging probes. DNA bipyramid nanostructures (DBNs), as a classic kind of DNA nanostructure, can be precisely constructed through the unparalleled base-pairing precision of oligonucleotide strands. DBNs were prepared by self-assembly of six oligonucleotides with equal molar amounts in a single annealing step, and purified by high performance liquid chromatography (HPLC). DBNs were stable in 10% FBS as well as 80% mouse serum for at least 8 h. To prepare 99mTc-labeled DBNs, N-hydroxysuccinimidyl S-acetylmercaptoacetyl triglycinate (Sacetyl-MAG3-NHS ester) tagged single-stranded DNA (ssDNA) was first radiolabeled with Tc-99m, and DBNs with an overhang were assembled and then hybridized with 99mTc-ssDNA to prepare 99mTc-labeled DNA bipyramid nanostructures (99mTc-MAG3-DBNs). DBNs were radiolabeled, with the radiochemical purity being over 90%. The plasma half-life of 99mTc-MAG3-DBNs in normal KM mice was about 6 min. The biodistribution and SPECT/CT imaging were conducted with 99mTc-MAG3-DBNs in KM mice, and both showed that 99mTc-MAG3-DBNs mainly concentrated in the intestine, liver, and kidneys, and there was also prominent uptake in the gallbladder and bladder. We successfully obtained a new class of SPECT molecular probes based on this DNA polyhedron structure.
研究领域:
核医学
·
分子影像
·
生物化学
·
放射学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2023
·Vol. 332
·期 6
·2093-2102
·
IF 1.6
Li Kehong,Fan Wenqi,Yan Jingxuan,Wang Jing,Zhao Peng,Liao Wei,Yang Yuchuan,Yang Xia,Wei Hongyuan,Chen Yue
Differences in cellular radiosensitivity and the binding affinity of radiopharmaceuticals could directly affect the radiotherapeutic effects. In this study, we investigated the radionuclide ( 177 Lu) induced radiosensitivity of serval non-small-cell lung cancer cells (NSCLCs) as well as the binding affinity of cetuximab to those cells. The apoptosis of NSCLCs caused by 177 Lu was related to the DNA double-strand damage and was cell-type dependent. We also proved that the introduction of 177 Lu to the antibody could enhance its cytotoxic effect on NSCLCs. The [ 177 Lu]Lu-DOTA-cetuximab could accumulate in the HCC827 tumor xenografts with excellent stability according to in vivo SPECT/CT imaging and the biodistribution results. The [ 177 Lu]Lu-DOTA-cetuximab showed high potential to be used for targeting diagnosis and radiotherapy in lung cancers.
研究领域:
肿瘤学
·
放射生物学
·
核医学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Xue Zhou,Ning Yan,Erik J. Cornel,Haidong Cai,Shaobo Xue,Hao Xi,Zhen Fan,Shisheng He,Jianzhong Du
We present a bone-targeting polymer vesicle with excellent single photon emission computed tomography/computed tomography (SPECT/CT) imaging capability and high antitumor drug delivery efficiency as an integrated platform for the simultaneous diagnosing and treatment of malignant bone tumors. This polymer vesicle can be self-assembled from poly( ε -caprolactone) 67 - b -poly[( L -glutamic acid) 6 - stat -( L -glutamic acid-alendronic acid) 16 ] (PCL 67 - b -P[Glu 6 - stat -(Glu-ADA) 16 ]), directly in water without the aid of a cosolvent . SPECT/CT dynamically tracked the drug distribution in the bone tumor rabbit models, and the tumor size was significantly reduced from >2.0 cm 3 to <0.6 cm 3 over 11 days. The pathological analysis demonstrated obvious necrosis and apoptosis of the tumor cells. Overall, this bone-targeting polymer vesicle provides us with a new platform for the combination of real-time diagnosis and therapy of malignant bone tumors.
研究领域:
药学
·
生物医学工程
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Yibin Yu,Chong Huang,Fen Chen,Weisan Pan,Ling Zhang
Integration of diagnostic and therapeutic modalities into a single nanoplatform can play an important role in personalized cancer therapy. In this work, an all-in-one theranostic nanoplatform (HPCT nanomicelles) for breast cancer was fabricated, composed of the synthetic polymer hyaluronan- b -poly(ε-caprolactone) (HA-PCL), drug curcumin (Cur) and adjuvant tocopheryl polyethylene glycol succinate (TPGS). HPCT nanomicelles presented adequate drug loading efficiency, excellent stability, and attractive hyaluronidase-sensitive release features. Imaging agent radionuclide 99m Tc was loaded into HPCT nanomicelles (denoted as 99m Tc-HPCT nanomicelles) and in vivo SPECT/CT imaging verified the HA-based nanomicelles could actively target breast cancer in mice. In vivo anti-tumor pharmacodynamic studies indicated that HPCT nanomicelles exhibited desirable anti-tumor efficacy with favorable biosafety. 99m Tc-HPCT nanomicelles, integrating imaging and therapeutic modalities, have the promising potential to be an all-in-one theranostic nanoplatform for breast cancer.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
诊断成像
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
·
2024
·Vol. 67
·期 11
·384-391
·
IF 0.9
Shuhua He,Lina Jia,Xiaobei Zheng,Yang Wang,Yuxia Liu,Lan Zhang
Programmed death-ligand 1 (PD-L1) expression is related to the efficacy and prognosis in triple-negative breast cancer. This study employed an indirect labeling method to synthesize [ 125 I]PI-Atezolizumab. The in vitro stability of [ 125 I]PI-Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [ 125 I]PI-Atezolizumab to MDA-MB-231 cells expressing humanized PD-L1 was assessed through in vitro incubation, yielding a K d value comparable to that of Atezolizumab. This suggests that the labeling process did not compromise the affinity of the Atezolizumab to PD-L1. Subsequently, pharmacokinetic studies were conducted in normal mice and biodistribution experiments in tumor-bearing mice. A comparison of the biodistribution results between [ 125 I]PI-Atezolizumab and 125 I-labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [ 125 I]PI-Atezolizumab for PD-L1 in MDA-MB-231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [ 125 I]PI-Atezolizumab, prepared via indirect labeling, for monitoring PD-L1 in triple-negative breast cancer models.
研究领域:
肿瘤学
·
分子影像学
·
放射性药物
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Xinyi Li,Yuyi Qian,Xin Lu,Mingzhen Xu,Simin He,Jianping Zhang,Shaoli Song
Transarterial radioembolization (TARE) is a recommended locoregional strategy for intermediate hepatocellular carcinoma (HCC), whereas, the effect is insufficient to reverse the immunosuppression tumor microenvironment, and the overall benefits for patients remain to be improved. In this study, a multifunctional microsphere (MS) 131 I-ICT/R848-MS is developed to propose an approach combined with TARE, icaritin (ICT) and immune modulator resiquimod (R848). ICT and iodine-131 ( 131 I) radiation can induce immunogenic cell death, which, in combination with R848, will boost dendritic cell (DC) maturation. Decellularized liver model and SPECT/CT imaging revealed high specificity and long retention of microspheres. Radioactive distribution of 131 I in tumor on 7 d following 131 I-MS injection was over 7 times of that in normal liver tissue (4.26 ± 1.21 % ID/g vs 0.57 ± 0.23 % ID/g). 131 I-ICT/R848-MS embolization brought significant immune activation, where the ratio of cytotoxic T lymphocytes to regulatory T cells in tumor sites upregulated from 1.75 ± 0.20 to 24.31 ± 1.79, and DC maturation in lymph nodes increased from 8.90 ± 1.51 % to 34.70 ± 3.12 %. Enhanced anti-tumor efficacy with no relapse was proved in rat orthotopic N1S1 HCC models. These results demonstrated the great potential of this multifunctional embolic agent to treat HCC through transarterial radio-immuno-chemoembolization (TARICE).
研究领域:
肿瘤学
·
放射肿瘤学
·
免疫疗法
·
医学影像
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）