1.Research progress of nuclear medicine imaging in detection of vulnerable atherosclerotic plaques
Hui TAN ; Dengfeng CHENG ; Hongcheng SHI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(4):367-370
Atherosclerosis is a vascular inflammatory disease.Vulnerable atherosclerotic plaques mainly lead to severe cardiovascular and cerebrovascular diseases,such as myocardial infarction and stroke.The research on the early diagnosis of vulnerable plaques becomes currently urgent.As a noninvasive molecular modality,the nuclear medicine imaging (with specific radiolabeled probes) has been used for the detection of unstable plaques,and for the evaluation of therapeutic effect of anti-atherosclerotic drugs.Nuclear imaging techniques for detecting metabolic activity,inflammation,hypoxia,angiogenesis,apoptosis,and microcalcification in unstable plaques are summarized in this review.
2.SP94 peptide as a specific probe for hepatocellular carcinoma imaging
Yanli LI ; Jie XIAO ; Yan HU ; Xiao LI ; Guobing LIU ; Yanzhao ZHAO ; Hui TAN ; Hongcheng SHI ; Dengfeng CHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2017;37(1):10-14
Objective To investigate the capability of 99 Tcm?tricine?EDDA/HYNIC?SFSIIHTPILPL ( SP94) as a specific probe for HCC imaging. Methods HYNIC?SP94 peptide was prepared by solid phase synthesis, followed by 99 Tcm labeling with tricine?EDDA as the coligand. After determination of radiochemical purity and stability, cell binding study was carried out by incubating Huh?7 cells with 99 Tcm?tricine?EDDA/HYNIC?SP94 at different specific activities (2.5, 4.0 and 30.0 GBq/μmol). The biodistribution studies and microSPECT/CT imaging were performed in Huh?7 tumor?bearing mice ( study group) and Hela tumor?bear?ing mice ( control group ) . Statistical analysis was by two?sample t test. Results 99 Tcm?tricine?EDDA/HYNIC?SP94 was synthesized with over 95% of labeling yield, which remained stable in saline and FBS up to 12 h. With increasing concentrations of 99 Tcm?tricine?EDDA/HYNIC?SP94, Huh?7 cell binding increased but became gradually saturated. In biodistribution studies, (1.02±0.26) %ID/g of tracer was accumulated in Huh?7 tumors at 0.5 h after injection of 99 Tcm?tricine?EDDA/HYNIC?SP94, higher than that in the HYNIC?SP94 blocking group ((0.34±0.09) %ID/g;t=3.537, P<0.05). Compared to Hela tumors, Huh?7 tumors were clearly visualized by microSPECT/CT, with which better imaging quality could be achieved with higher specific radioactivity. Conclusion 99 Tcm?tricine?EDDA/HYNIC?SP94 could achieve a high labeling effi?ciency and good in vitro stability as a potential diagnostic tracer specifically targeted for HCC.
3.Comparation and considerations for general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia
ZHU Jia ; LOU Yongjun ; PAN Fangfang ; GENG Xiaoting ; TANG Dengfeng ; SHANG Yue ; ZHENG Jinqi ; ZHENG Cheng ; TAO Qiaofeng
Drug Standards of China 2024;25(1):035-040
Objective: The characteristics and differences of the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia were investigated to provide references and suggestions for the compilation of the Chinese Pharmacopoeia.
Methods: From the perspective of frame structure and main contents, the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia was compared.
Results: Each volume of the Chinese Pharmacopoeia had its general notice, including 34 to 48 items and 10 to 12 chapters based on different varieties collected in each volume. The Japanese Pharmacopoeia had 49 items not arranged by chapters. There are many differences on the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia, such as the definitions and expressions of names, determination of appearance, revision rules, risk assessment and quality control conception. The framework of the general notice in the Chinese Pharmacopoeia was clear, the content was specific and the operation was friendly. The term description of the general notice in the Japanese Pharmacopoeia was concise, and some terms need to be implemented under the guidance of professional knowledge.
Conclusion: In light of comparative study, every volume’s general notice of the Chinese Pharmacopoeia has its own characteristics. By integrating advanced analytical technique, combining the requirements with laws and regulations, and optimizing content and terms, all volume’s general notice could be explored to be coordinated and unified.
4.Research progress in metabolic and receptor-like nuclear imaging agents for hepatocellular carcinoma
Yanli LI ; Guobing LIU ; Dengfeng CHENG ; Hongcheng SHI
Chinese Journal of Hepatology 2016;24(8):619-623
Hepatocellular carcinoma (HCC) commonly presents with high morbidity and mortality,and early staging diagnosis and timely treatment is pivotal to prolonging patients' survival time.Compared with traditional morphological imaging methods such as ultrasound,computed tomography (CT),and magnetic resonance imaging (MRI),functional imaging methods like single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are playing an increasingly important role in the early diagnosis,efficacy assessment,prognostic evaluation,and treatment planning for HCC,thanks to their higher sensitivity at a molecular level by using various radiopharmaceuticals.
5.Preparation of 68Ga labeled pre-targeted molecular probe based on bio-orthogonal Diels-Alder click chemistry and CD11b receptor targeted imaging in CT26 colon cancer mouse models
Yinging ZHANG ; Dai SHI ; Zhan XU ; Yuan CHENG ; Dengfeng CHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(10):585-591
Objective:To prepare a 68Ga labeled probe targeting integrin alpha M(CD11b) receptor, namely 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid-Glycine-Arginine-Glutamate-Arginine-Glutamate-polyethylene glycol 11-1, 2, 4, 5-terazine/CD11b antibody-F(ab′) 2-trans-cyclooctene ( 68Ga-NOTA-Polypeptide-PEG 11-Tz/anti-CD11b-F(ab′) 2-TCO), and to explore its feasibility as a molecular probe for CD11b receptor through microPET imaging. Methods:Immunofluorescence was used to detect the expression of CD11b on the surface of RAW264.7 cell. CD11b specific monoclonal antibody (M1/70) was conjugated with TCO, and anti-CD11b-F(ab′) 2-TCO fragment was obtained. The ligand NOTA-Polypeptide-PEG 11-Tz was labeled with 68Ga, and its specific activity and radiochemical purity were detected. Pre-targeted cell binding experiment was conducted to evaluate the binding ability of molecular probe. CT26 colon cancer bearing mouse models were established, and then pre-targeted biodistribution and imaging experiments were performed. Immunohistochemical experiment was used to verify the expression of CD11b receptor in tumor. The one-way analysis of variance was used to compare the data. Results:The results of immunofluorescence demonstrated CD11b receptor was highly expressed on the surface of RAW264.7 cell. Anti-CD11b-F(ab′) 2-TCO fragment was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). 68Ga-NOTA-Polypeptide-PEG 11-Tz was successfully synthesized, with the labeling efficiency of 94.6%. The specific activity was 7.0-7.4 MBq/μg, and the radiochemical purity was higher than 95%. Pre-targeted cell binding experiment confirmed that the molecular probe bound to the CD11b receptor. The biodistribution and imaging experiments showed that the kidney radioactivity uptake was high at pre-targeted 4, 12 and 24 h intervals, which proved that probe was excreted through the urinary system. In addition, molecular probe had higher radioactive uptake at the tumor site, with the tumor/muscle ratios of 9.23±1.45, 12.53±1.36 and 10.74±1.11 ( F=848.8, P<0.05). When the radioligand was injected 1 h after the pre-positioned 12 h interval, the images contrast was the best, with the standardized uptake value (SUV) in tumor and muscle of 0.67±0.12, 0.09±0.04, respectively. Immunohistochemistry verified the highly expression of CD11b receptor in tumor. Conclusions:The pre-targeted molecular probe 68Ga-NOTA-Polypeptide-PEG 11-Tz/anti-CD11b-F(ab′) 2-TCO is successfully synthesized. The molecular probe has targeting ability for CD11b + colon cancer, and is expected to be used as a tracer targeting CD11b receptor in vivo.
6.MicroPET imaging studies of 89Zr-labeled EGFR and HER2 antibodies in gastric mucinous adenocarcinoma
Dai SHI ; Qinghui CAO ; Yingying ZHANG ; Yuan CHENG ; Zhan XU ; Dengfeng CHENG ; Hongcheng SHI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(10):597-601
Objective:To screen 89Zr-labeled anti-epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) monoclonal antibody molecular probes suitable for monitoring the gastric mucinous adenocarcinoma bearing mouse models with low glucose metabolism. Methods:The expression of EGFR and HER2 in the MGC803 gastric cancer cell line was verified by analyzing cell slides and xenograft tumor sections. 89Zr-Deferoxamine (DFO)-Cetuximab and 89Zr-DFO-Pertuzumab were prepared and the radiochemical purity was detected. Cell binding experiments and blocking experiments were performed to verify the binding ability and specificity of the probes. Twelve gastric mucinous adenocarcinoma bearing mouse models were divided into 3 groups ( n=4 in each group): 89Zr-DFO-Cetuximab group (7.4 MBq/mouse, 74 μg/mouse), 89Zr-DFO-Pertuzumab group (7.4 MBq/mouse, 70 μg/mouse) and 18F-fluorodeoxyglucose (FDG) group (7.4 MBq/mouse). MicroPET imaging was performed at 4, 24 and 48 h ( 18F-FDG group underwent imaging at 1 h only) post-injection. The biodistribution study of 89Zr-DFO-Cetuximab and 89Zr-DFO-Pertuzumab was conducted in 2 groups ( n=4 in each group) 48 h after the injection. The independent sample t test was used for data analysis. Results:The immunofluorescent staining demonstrated EGFR expression was significantly higher than HER2 expression in MGC803 gastric cancer cell line. The radiochemical purity of 89Zr-DFO-Cetuximab and 89Zr-DFO-Pertuzumab were both more than 95%, and the specific activities were 100 and 95 MBq/mg, respectively. The two probes had good stability in normal saline and fetal bovine serum, with the radiochemical purity higher than 80% at 72 h. MicroPET imaging showed that the uptake of 89Zr-DFO-Cetuximab in the MGC803 tumor was significantly higher than that of 18F-FDG and 89Zr-DFO-Pertuzumab. The biodistribution study demonstrated the 89Zr-DFO-Cetuximab uptake (percentage activity of injection dose per gram of tissue, %ID/g) of tumors at 48 h was significantly higher than that of 89Zr-DFO-Pertuzumab (56.3±12.0 vs 22.0±3.6; t=4.31, P<0.05). Conclusion:Compared with 89Zr-DFO-Pertuzumab, 89Zr-DFO-Cetuximab has a better potential for non-invasive monitoring of gastric mucinous adenocarcinoma with low glucose metabolism.
7.Acupuncture Regulates the Balance of CD4 T Cell Subtypes in Experimental Asthma Mice.
Ming DONG ; Wen-Qian WANG ; Juan CHEN ; Mi-Hui LI ; Fei XU ; Jie CUI ; Jing-Cheng DONG ; Ying WEI
Chinese journal of integrative medicine 2019;25(8):617-624
OBJECTIVE:
To evaluate the involvement of different CD4 T cell subtypes in the anti-asthmatic effects of acupuncture in asthmatic mice.
METHODS:
BALB/c mice were challenged by ovalbumin (OVA) for the establishment of experimental asthma model. Mice were divided into 4 groups by a random number table including the normal control, asthma model, acupuncture and sham acupuncture groups (14 per group). Acupoints Dazhui (GV 14), bilateral Fengmen (BL 12) and Feishu (BL 13) were selected for manual acupuncture treatment every other day for 4 weeks and Huantiao (GB 30) was selected for sham acupuncture. Airway hyperresponsiveness was examined by Buxco Pulmonary System. Pulmonary histopathology analysis was performed for inflammatory cell infiltration and mucus hypersecretion by haematoxylin eosin staining and periodic acid-Schiffstaining. Inflammatory mediators assays of serum were investigated by enzyme-linked immunosorbent assay and Bio-Plex. CD4 T cell subpopulations including the expression levels of important factors in T lymphocyte polarization in lung tissue were examined by flow cytometric and Western blot analyses. Related pathways were detected by Western blot assay.
RESULTS:
Compared with the OVA-induced asthma model group, acupuncture could attenuate airway hyperresponsiveness, inhibit inflammatory cell infiltration and mucus hypersecretion (P<0.05 or P<0.01). Furthermore, acupuncture increased the expressions of T-bet and Foxp3, the cell numbers of CD4 interferon gamma (IFN-γ) and CD4 Foxp3 in lung tissue and the level of Treg type cytokine interleukin (IL)-10 in serum (P<0.05 or P<0.01). Meanwhile, acupuncture reduced the RAR-related orphan receptor gamma t (RORγt) level, the cell numbers of CD4 IL-17A as well as the levels of IL-5, IL-13 and IL-17A in serum (P<0.05 or P<0.01). In addition, both acupuncture and sham acupuncture could inhibit the phosphorylation of p38 and p44/42 (P<0.01).
CONCLUSION
Acupuncture could alleviate allergic airway inflammation by strengthening the activities of Th1 and Treg, thus regulating the balance of CD4 T cell subtypes in experimental asthmatic mice.
8.Imaging study of 18F-SDM-8 in rat temporal lobe epilepsy model
Zhequan FU ; Qingyu LIN ; Lu LIU ; Zhan XU ; Hongcheng SHI ; Dengfeng CHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(1):36-41
Objective:To explore whether the specific synaptic vesicle glycoprotein 2A (SV2A) targeted imaging agent ( R)-4-(3-fluoro-5-(fluoro- 18F)phenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one ( 18F-SDM-8) can be used to detect epileptic foci. Methods:Twenty male Sprague-Dawley (SD) rats (8-9 weeks) were injected with 1.2 μl of kainic acid (16 rats in the epilepsy group) or saline (4 rats in the control group) into the right hippocampus. 18F-SDM-8 and 18F-FDG mircoPET/CT imaging were respectively performed at 1-2 d (acute phase), 6-7 d (incubation period) and 45-60 d (chronic phase) after the seizure. Asymmetric index (AI) was used to evaluate the epileptic foci identify ability of 18F-SDM-8. Paired t test, Mann-Whitney U test and Pearson correlation analysis were used to analyze data. Results:In the three periods of 18F-SDM-8 imaging, the differences of AI of hippocampus between the epilepsy group and control group were statistically significant ( z values: from -2.64 to 2.67, all P<0.05). Both imaging agents had asymmetric uptake in the epilepsy group (right was lower than left), and the decrease in the medial right temporal lobe was the most significant. The pathological staining results were consistent with the imaging results. In the chronic phase of the epilepsy group, the differences of 18F-SDM-8 SUV mean (right versus left) in each brain area of interest were statistically significant ( t value: from -33.40 to -5.60, all P<0.05). The asymmetric uptake of the two imaging agents in the hippocampus had a better correlation ( r=0.97, P=0.001), and the AI of 18F-SDM-8 ((34.2±8.4)%) in this area was 1.4 times higher than that of 18F-FDG ((24.6±4.7)%). Conclusions:18F-SDM-8 PET is a promising method to test the level of SV2A. It can reflect the changes of SV2A in the rat epilepsy model induced by intrahippocampal injection of kainic acid, and improve the sensitivity of molecular imaging for epileptic foci.
9.Development of nuclide targeted matrix metalloproteinase inhibitors in atherosclerotic plaque imaging
Yan HU ; Dengfeng CHENG ; Hongcheng SHI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2019;39(1):45-48
Atherosclerotic vulnerable plaques may cause acute cardiovascular events.Matrix metalloproteinase (MMP) plays an important role in the pathological process of high-risk plaques.It degrades the extracellular matrix of atherosclerotic plaque,thus making the fibrous cap thinner and the plaque more vulnerable,which lead to rupture.MMP inhibitors (MMPI) can specially bind MMP and inhibit its activity.Taking MMP as the target,nuclear medical imaging can identify and evaluate the unstable plaque in molecular level,and can also be used to explore the biological characteristics of plaque,as well as to monitor drug efficiency.This review summarizes the development of nuclide targeted MMPI in atherosclerotic plaque imaging.
10.Research on the present situation of detection strategies for infectious markers related to transfusion transimission in China
Wei TAN ; Shengyan YING ; Ning CHENG ; Yujun LI ; Xiaoli CHEN ; Fang WANG ; Yang ZHANG ; Xiaojie LIU ; Lin BAO ; Yong DUAN ; Chen MA ; Chunlan LIU ; Dengfeng WANG ; Zhijun ZHEN ; Li LI ; Jian ZHANG ; Ranran LU ; Peng WANG ; Mingxia LI ; Xinli JIN ; Xiaobo CAI ; Mei YU ; Jianling ZHONG ; Lili ZHU ; Jianping LI
Chinese Journal of Experimental and Clinical Virology 2023;37(4):383-388
Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.