Shuang Liu

Ehime University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

David S. Edwards

Texas Tech University

Young‐Seung Kim

National Institutes of Health

Jiyun Shi

Chinese Academy of Sciences

Wen‐Yuan Hsieh

National Health Research Institutes

Fan Wang

Institute of Biophysics

Yang Zhou

Sanya University

Bing Jia

Peking University

Wei Fang

Chinese Academy of Medical Sciences & Peking Union Medical College

Zhaofei Liu

Peking University

Anthony R. Harris

University of Prince Edward Island

Cooperative Institutions

Bristol-Myers Squibb (United States)

Chinese Academy of Medical Sciences & Peking Union Medical College

Purdue University West Lafayette

DuPont (United States)

Chinese Academy of Sciences

Peking University

Sun Yat-sen University

China Medical University

Nanjing Medical University

Chongqing Medical University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Integration of IgA and IgG Autoantigens Improves Performance of Biomarker Panels for Early Diagnosis of Lung Cancer

Molecular & Cellular Proteomics (2020)

Jianbo Pan Lili Yu Qingwei Wu Xiaoqing Lin Shuang Liu

Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (

Isotype

Biomarker Discovery

Immunoglobulin M

10.1074/mcp.ra119.001905

Cite

Citations (26)

Novel 99m Tc(III)-azide complexes [ 99m Tc(N 3 )(CDO)(CDOH) 2 B-R] (CDOH 2 = cyclohexanedione dioxime) as potential radiotracers for heart imaging

Nuclear Medicine and Biology (2016)

Min Liu Yumin Zheng Uğur Avcıbaşı Shuang Liu

Biodistribution

10.1016/j.nucmedbio.2016.05.001

Cite

Citations (10)

Expression levels of integrin αvβ3 versus tumor uptake of 99mTc-labeled RGD peptide

Journal of Nuclear Medicine (2009)

Bing Jia Zhaofei Liu Jiyun Shi Huiyun Zhao Shuang Liu

272 Objectives Radiolabeled cyclic RGD peptides are integrin αvβ3-specific. We evaluated the tumor uptake of 99mTc-labeled new cyclic RGD dimer against the expression levels of integrin αvβ3. Methods A new cyclic RGD peptide, G3-E[PEG4-c(RGDfK)]2, was synthesized and labeled with 99mTc (99mTc-G3-2PEG4 dimer). The integrin αvβ3 expression of U87MG human glioma cells and HT29 human colon cancer cells, as well as the corresponding tumor tissues was investigated by immunofluorescent staining. The affinity of HYNIC-G3-2PEG4 dimer and HYNIC-dimer to integrin αvβ3 was compared by cell binding assay. Biodistribution and imaging studies were carried out in both U87MG and HT29 tumor models. Results U87MG cells highly expressed integrin αvβ3, whereas HT29 cells did not express integrin αvβ3. The tissue staining showed that U87MG tumors expressed both human and murine integrin αvβ3, whereas HT29 tumors expressed only murine integrin αvβ3 around the neovasculature. The IC50 values were 8.1±1.2 nM for HYNIC-dimer and 3.4±0.7 nM for HYNIC-G3-PEG4 dimer, indicating the higher affinity of new RGD dimer than the former RGD dimer. The tumor uptake of 99mTc-G3-2PEG4 dimer in U87MG tumors was much higher than that in HT29 tumors (6.82±1.71 vs 2.55±0.58, and 4.62±1.45 vs 1.66±0.33 %ID/g at 0.5 and 2 h p.i, respectively). Compared to HT29 tumors, the images of U87MG tumors were much more clear. Conclusions The tumor uptake of 99mTc-RGD peptide depends on the expression levels of integrin αvβ3. The quantitive correlation analyzed by Western blot is in progress.

Biodistribution

D-dimer

Source

Cite

Citations (0)

Ascorbic Acid: Useful as a Buffer Agent and Radiolytic Stabilizer for Metalloradiopharmaceuticals

Bioconjugate Chemistry (2003)

Shuang Liu Charlie E. Ellars David S. Edwards

The goal of this study is to explore the use of ascorbic acid (AA) as a buffer agent and a radiolytic stabilizer for preparation and stabilization of radiolabeled DOTA-biomolecule conjugates. Results from a titration experiment show that 0.1 M AA solution has sufficient buffer capacity at pH 5.0 while 0.5 M AA solution is useful even at pH 6.0. The radiolabeling experiment using TA138, a DOTA-conjugated nonpeptide integrin alpha(v)beta(3) receptor antagonist, clearly demonstrates that AA is a good buffer agent for pH control and an excellent antioxidant for stabilization of metal-labeled diagnostic ((111)In) and therapeutic ((90)Y and (177)Lu) radiopharmaceuticals if the radiolabeling is performed at pH 5-6. There is no need for the additional stabilizer (e.g., gentisic acid) and buffer agent such as ammonium acetate. The anaerobic AA formulation described in this study is particularly useful for radiolabeling of small biomolecules, which are sensitive to the radiolytic degradation during radiolabeling.

Reducing agent

Stabilizer (aeronautics)

Buffer (optical fiber)

Biomolecule

Gentisic acid

Perchloric acid

10.1021/bc034109i

Cite

Citations (62)

Effects of Targeting Moiety, Linker, Bifunctional Chelator, and Molecular Charge on Biological Properties of ⁶⁴Cu-Labeled Triphenylphosphonium Cations

Journal of Medicinal Chemistry (2008)

Young-Seung Kim Chang‐Tong Yang Jianjun Wang Lijun Wang Zibo Li

In this report, we present the synthesis and evaluation of six new 64Cu-labeled triphenylphosphonium (TPP) cations. Biodistribution studies were performed using the athymic nude mice bearing U87MG human glioma xenografts to explore the impact of TPP moieties, linkers, bifunctional chelators (BFCs), and molecular charge on biological properties of 64Cu radiotracers. On the basis of the results from this study, it is concluded that (1) mTPP (tris(4-methoxyphenyl)phosphonium) is a better mitochondrion-targeting molecule than TPP and 3mTPP (tris(2,4,6-trimethoxyphenyl)phosphonium); (2) DO3A (1,4,7,10-tetraazacyclododecane-4,7,10-triacetic acid) and DO2A (1,4,7,10-tetraazacyclododecane-4,7-diacetic acid) are suitable BFCs for the 64Cu-labeling of TPP cations; (3) NOTA-Bn (S-2-(4-thioureidobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid) has a significant adverse effect on the radiotracer tumor uptake and tumor-to-background ratios; and (4) monoanionic BFCs should be avoided to ensure that 64Cu chelate has a neutral or negative charge. Considering the tumor uptake and tumor/liver ratios, 64Cu(DO2A-xy-TPP)+ is the best candidate for more extensive evaluations in different tumor-bearing animal models.

Biodistribution

Moiety

Phosphonium

Linker

10.1021/jm7015045

Cite

Citations (68)

Improved Tumor Targeting of Radiolabeled RGD Peptides Using Rapid Dose Fractionation

Cancer Biotherapy and Radiopharmaceuticals (2004)

Marcel Janssen Cathelijne Frielink Ingrid Dijkgraaf Wim J.G. Oyen David S. Edwards

10.1089/1084978041979634

Cite

Citations (21)

Clinical study of 99mTc-3P-RGD2 peptide imaging in osteolytic bone metastasis

Oncotarget (2017)

Guoqiang Shao Wei Gu Muhong Guo Shiming Zang Jinjing Fu

To investigate the value of integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3P-RGD2) as a radiotracer in dectecting osteolytic bone metastases.This is a retrospective study involving a cohort of 69 consecutive patients including 59 with lung cancer and 10 with other cancers. Patients were required to receive whole body scan (WBS) and regional SPECT/CT imaging with 99mTc-3P-RGD2 (RGD imaging) and 99mTc-MDP (MDP imaging) as a radiotracer successively within days. Final diagnosis was based on comprehensive assessment of all available data including case history, CT, MRI, SPECT/CT, PET/CT, histopathology and 6-12 months follow-up. Visual observation and semiquantitative analysis (T/N: tracer uptake ratio of osteolytic metastases to normal bone) of 99mTc-3P-RGD2 or 99mTc-MDP imaging were performed and their detective values for osteolytic metastases were compared.A total of 131 osteolytic metastatic lesions were retrospectively studied. Osteolytic metastases mainly presented as "hot region", occasionally as "cool or normal region" on RGD imaging. The detection sensitivity of RGD WBS for osteolytic metastases was significantly higher than that of 99mTc-MDP WBS (80.9% vs. 46.6%, p<0.01). The sensitivity increased to 96.2% (126/131) when combining with SPECT/CT. 99mTc-3P-RGD2 imaging also promoted the detection of unknown primary tumor, lymph node metastases and offered information for clinical staging. T/N of 99mTc-3P-RGD2 in lung adenocarcinoma osteolytic metastases showed no statistical difference compared with that in squamous-cell carcinoma (6.84±3.46 vs. 7.33±3.22, t = 0.39, p = 0.71). Whereas, it was higher in osteolytic metastases from lung cancer than that from thyroid cancer (7.05±3.01 vs. 4.11±2.67, p = 0.03).99mTc-3P-RGD2 peptide imaging showed great potential for detection of osteolytic bone metastasis due to high expression level of integrin αvβ3 on osteoclast and most tumor cells.

10.18632/oncotarget.17486

Cite

Citations (14)

Novel Approach for ^99mTc-Labeling of Red Blood Cells: Evaluation of ^99mTc-4SAboroxime as a Blood Pool Imaging Agent

Bioconjugate Chemistry (2017)

Min Liu Zuoquan Zhao Wei Fang Shuang Liu

Angiography with radiolabeled red blood cells (RBCs) plays an important role in diagnosis and prognosis in vascular diseases. Both in vitro and in vivo methods have been developed for 99mTc-labeling of RBCs. However, these methods are complicated and lack reproducibility. Therefore, it is highly desirable to develop an alternative method for routine 99mTc-labeling of RBCs. In this report, we present a novel approach for 99mTc-labeling of RBCs. We prepared a new 99mTc(III) radiotracer [99mTcCl(CDO)(CDOH)2B-4AS] (99mTc-4ASboroxime: 4AS-B(OH)2 = 4-aminosulfonylphenyl)boronic acid, and CDOH2 = cyclohexanedione dioxime) in >95% radiochemical purity. Imaging and biodistribution studies were performed in Sprague-Dawley (SD) rats. It was found that the blood radioactivity was ∼6.0%ID/g (∼90% injected dose for 200-225 g SD rats) for 99mTc-4ASboroxime with low uptake in the myocardium, kidneys, liver, lungs, and muscle, most likely due to lack of leakage of 99mTc-labeled RBCs from the intravascular space. The blood radioactivity was almost unchanged over the 2 h period, suggesting that the binding of 99mTc-4ASboroxime to blood components (cells, proteins, and plasma) is stable. The results from γ-counting of the isolated blood components showed that 99mTc-4ASboroxime had >95% of blood radioactivity binding to RBCs, ∼1% to albumin, and ∼3% remaining free in blood plasma, demonstrating its RBC-specificity. The results from imaging studies in SD rats indicated that 99mTc-4ASboroxime is predominantly distributed in the blood pool. Main blood vessels were well delineated in the head/neck and abdominal regions. This statement was further substantiated by the results from imaging studies in pigs. 99mTc-4ASboroxime is an excellent blood pool agent with the potential for diagnosis and prognosis of vascular diseases.

Biodistribution

Technetium-99m

Imaging agent

10.1021/acs.bioconjchem.7b00601

Cite

Citations (7)

[Expression of alpha subunit for IL-6 receptor at mRNA and protein levels in human leukemic cells].

PubMed (2002)

Shuang Liu Yongzhi Xi Siqi Guo Nan Liu Fei Liang

To probe into the expression of alpha subunit for IL-6R at both mRNA and protein levels in human leukemic cells and to discuss its implication in targeted treatment for leukemia with recombinant IL-6-PE40 exotoxin fusion protein mediated by IL-6/IL-6R system, semi-quantitative RT-PCR, sequencing and FCM were used to analyze the gene and protein expression levels of alpha subunit for IL-6R in leukemic cells. Our results showed that not only mRNA but also protein of alpha subunit for IL-6R are highly expressed in the myelogenous leukemic cell lines, the relative expression levels of mRNA were KG-1(1.22) > (1.02) > U266(1.00) > U937(0.99) > HL-60(0.76). Among lymphoblastic leukemic cell lines, Raji expressed a certain amount of alpha subunit mRNA (0.77), whereas its alpha subunit protein was not detected. Expression of alpha subunit mRNA and protein were negative in lymphoblastic leukemic cell lines, HuT28 and CEM, and chronic myelocytic leukemic cell line K562. These results correlate with those of FCM highly. Noteworthily, normal human peripheral blood mononuclear cells expressed hardly protein of IL-6R alpha subunit. So this study provides sufficient experimental evidence that the targeted treatment by recombinant IL-6-PE40 can specifically kill leukemic cells highly expressing IL-6R without toxicity to normal hematopoietic cells.

SCN3A

K562 cells

Source

Cite

Citations (0)

Pyridine-Containing 6-Hydrazinonicotinamide Derivatives as Potential Bifunctional Chelators for ^99mTc-Labeling of Small Biomolecules

Bioconjugate Chemistry (2004)

Ajay Purohit Shuang Liu Charlie E. Ellars Dave Casebier Stephen B. Haber

As a continuation of our interest in novel 99mTc chelating systems, several pyridine-containing HYNIC (6-hydrazinonicotinamide) derivatives (L1-L5) have been synthesized and characterized by NMR (1H and 13C) and LC-MS. 99mTc complexes of L1-L5 were prepared by the reaction of the HYNIC derivative with 99mTcO4- in the presence of excess tricine and stannous chloride. Results from this study show that the attachment site of the linker is critical for the formation of macrocyclic 99mTc complexes. For example, the pyridine-N in L3 is not able to bond to the Tc, because the lysine linker is attached to the 4-position. When the linker is at the 2-position, L1 forms the macrocyclic complex [99mTc(L1)(tricine)], but the radiochemical purity is relatively low. If the linker is attached to the 3-position of the pyridine ring, the HYNIC derivatives form macrocyclic complexes [99mTc(L)(tricine)] (L2, L4, and L5) in high yield (>95%). The HPLC data suggest that the macrocyclic complex [(99m)Tc(L2)(tricine)] exists in solution as four isomers: two diastereomers and two conformational isomers. Diastereomers are due to a combination of the chirality of the lysine linker and of the Tc chelate. Replacing lysine with a pentamethylenediamine linker results in the macrocyclic complex [99mTc(L4)(tricine)] with two conformational isomers, which interconvert rapidly at room temperature. Changing the linker from pentamethylenediamine to hexamethylenediamine did not eliminate the minor isomer; but the percentage of the minor isomer was reduced from approximately 10% for [99mTc(L4)(tricine)] to only 6% for [99mTc(L5)(tricine)]. The linker length is an important parameter to minimize the minor isomer. LC-MS data of complexes [99mTc(L)(tricine)] (L2, L4, and L5) are completely consistent with their proposed compositions. On the basis of these data, it is concluded that pyridine-containing HYNIC derivatives have the potential as bifunctional chelators for 99mTc-labeling of small biomolecules if the linker is attached to the 3-position of the pyridine ring.

Linker

Diastereomer

Tricine

Chirality

10.1021/bc034141c

Cite

Citations (16)