2017 Vol. 41, No. 2

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ORIGINAL ARTICLES
New permeable hydrogel for tumor radiotherapy in situ
Fan Huang, Yang Gao, Yumin Zhang, Lijun Yang, Liping Chu, Jinjian Liu
2017, 41(2): 81-87. doi: 10.3760/cma.j.issn.1673-4114.2017.02.001
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ObjectiveTo design and synthesize a novel permeable hydrogel loaded with a radiation agent for the implantation radiotherapy of tumors.MethodsThe polymer PECT-RGD[PECT:poly(ε-caprolactone-co-1, 4, 8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1, 4, 8-trioxa[4.6]spiro-9-undecanone); RGD:Arg-Gly-Asp] was synthesized by esterification reaction, and an 131I-labeled hyaluronic acid was prepared by amidation reaction and chloramine-T method. The chemical structure of them was characterized by 1H-NMR, and the 131I-labeled hyaluronic acid was isolated and purified by precipitation and centrifugation. Hydrogel formation was verified by vial flipping experiment, and the cytotoxicity of the polymer materials was evaluated by MTT assay. The in vivo stability and degradation of the injected hydrogel were studied using a radioactive small animal live imaging system. The in vivo antitumor effect of the 131I@PECT-RGD hydrogel was investigated by inhibiting tumor growth volume and tumor tissue section.ResultsThe polymer PECT-RGD was non-cytotoxic and could form a stable hydrogel under the normal physiological temperature(37℃). This hydrogel is capable of self-degradation in vivo. Compared with the PBS group, the 131I@PECT-RGD hydrogel and the 131I@PECT gel showed significantly higher anti-tumor efficiency (P < 0.05, F=71.968). A significant difference in anti-tumor efficiency was found between the 131I@PECT and 131I@PECT-RGD hydrogels (P < 0.05, t=7.276). No significant difference in body weight was found among the three groups (P > 0.05, F=3.878). HE staining showed that only a small part of the tumor tissue was necrotic in the PBS group, whereas a large part of the tumor tissue was necrotic in the 131I@PECT group; the tumor tissue of the 131I@PECT-RGD group was generally necrotic.ConclusionsThe 131I@PECT-RGD hydrogel could be injected into tumor tissue in situ and display great biocompatibility, self-degradation ability, and anti-tumor activity. Thus, this hydrogel has potential applications in local radiotherapy.
Construction of 131I-labeled and dual-drug loaded multifunctional nanoparticles
Yueqian Zhang, Renfei Wang, Qiang Jia, Hanjie Wang, Ruiguo Zhang, Jian Tan, Jin Chang
2017, 41(2): 88-93. doi: 10.3760/cma.j.issn.1673-4114.2017.02.002
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ObjectiveTo construct 131I-labeled and dual-drug-loaded multifunctional mesoporous silica(mSiO2) nanoparticles, and to investigate its characteristics, drug release kinetics, and uptake by anaplastic thyroid cancer(ATC) cells.MethodsThe mSiO2 nanoparticles were constructed through the conventional template method. 17-allylamino-17-demethoxygeldanamycin(17-AAG) and Torin2 were loaded at equal concentrations, and bovine serum albumin was connected to the amino-modified nanoparticles. The characteristics, encapsulation efficiency, and drug loading rates of the nanoparticles were then investigated. Drug release was analyzed by high-performance liquid chromatography. The nanoparticles were labeled with 131I using the chloramine-T method. The time-dependent cellular uptake of 131I-labeled nanoparticles was also analyzed to evaluate the uptake and retention of the nanoparticles in ATC cells. T'-test was used for data analysis using SPSS19.0 software.ResultsThe mSiO2 nanoparticles and (17-AAG+Torin2)@mSiO2-BSA-131I samples were successfully constructed. The average diameters were 170 nm to 250 nm and 200 nm to 300 nm, respectively, with good dispersibility and spherical shape. The labeling rate and radiochemical purity of the 131I-nanoparticles were 66.31% to 78.25% and 98.80% to 99.42%, respectively. The drug loading rates of 17-AAG and Torin2 were 7.31%±0.22% and 6.04%±0.79%, and their encapsulation efficiencies were 86.21%±1.32% and 85.17%±2.05%, respectively. The nanoparticles loaded with 17-AAG and Torin2 exhibited slow drug release behavior. The uptake of(17-AAG+Torin2)@mSiO2-BSA-131I was higher than that of Na131I(t=32.63-109.31, all P < 0.01) and could reach its maximum level at 3 h after incubation.ConclusionsThe mSiO2 nanoparticles loaded with 17-AAG and Torin2 and labeled with 131I exhibited slow drug release behavior. ATC cells could uptake(17-AAG+Torin2)@mSiO2-BSA-131I rapidly.
Clinical value of 18F-FDG PET/CT in cancer of unknown primary
Minshan Jin, Jun Zhang, Yiyi Jiang, Chunlei Dai, Jinfeng Liang
2017, 41(2): 94-97, 149. doi: 10.3760/cma.j.issn.1673-4114.2017.02.003
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ObjectiveTo evaluate the clinical value of 18F-FDG PET/CT whole-body imaging in the manage-ment of cancer of unknown primary(CUP).MethodsFrom February 2015 to June 2016, 46 CUP patients were analyzed retrospectively in Taizhou People's Hospital. They underwent 18F-FDG PET/CT imaging to detect their primary tumors that had not been detected through routine examinations. Visual and semiquantitative analyses were then employed to analyze the PET/CT images. The results were assessed on the basis of the pathological results, comprehensive clinical diagnoses, and clinical follow-ups.ResultsOf the 46 patients, 33 had primary tumors, which were detected through 18F-FDG PET/CT imaging and further confirmed by pathology or clinical follow-up. Meanwhile, the primary tumors in 13 patients were not characterized. The CUP detection rate of the 18F-FDG PET/CT was 71.7%(33/46). Of the 33 patients with detected CUPs, 3 had lymphoma, 2 had gastric cancer, 4 had esophageal cancer, 3 had oophoroma, 14 had lung cancer, 2 had liver cancer, 1 had urinary tract epithelial cancer, 2 had nasopharyngeal carcinoma, 1 had multiple myeloma, and 1 had colon cancer. The modes of tumor metastasis included lymphatic metastasis in 32 cases, bone metastasis in 20 cases, liver metastasis in 13 cases, lung metastasis in 9 cases, pleural and peritoneal metastasis in 5 cases, adrenal metastasis in 3 cases, brain metastasis in 4 cases, subcutaneous metastasis in 3 cases, and pericardium metastasis in 1 case.ConclusionsThe 18F-FDG PET/CT outperforms ordinary routine examinations in terms of CUP detection. Thus, 18F-FDG PET/CT possesses significant importance to clinical management.
Follow-up study on children and adolescents with Graves hyperthyroidism after 131I treatment
Fanhui Yang, Yue Chen, Chunyin Zhang
2017, 41(2): 98-102. doi: 10.3760/cma.j.issn.1673-4114.2017.02.004
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ObjectiveTo investigate the therapeutic effects and safety of 131I treatment on children and adolescents with Graves disease.MethodsIn this study, 89 children and adolescents with Graves hyperthyroidism cases were treated using 131I. 131I was given at a dosage of 2.59 to 4.44 MBq per gram of thyroid tissue and calibrated according to the course of disease, thyroid weight, and the highest iodine rate. The treatment was via oral medication on an empty stomach once a day. All cases were required to undergo a proper medical follow-up at the end of 3, 6, and 12 months after treatment and once a year later. The cure, hypothyroidism rates and incidence rates of benign and malignant thyroid tumors and the health of their offspring were studied. The safety of radioiodine treatment for children and adolescents'growth, development were also evaluated.ResultsFollow-up was conducted on 80 cases, with 30 males and 50 females, aged from 6 to 19(12.2±2.3) years; nine patients were lost to follow-up(10.1%). The maximum dose of 131I ranged from 177.6 to 555 MBq per patient; the mean dose was 203.5 MBq. After one year of radioiodine treatment, the cure rate was 82.50%, and the effective rate was 98.75%; no efficiency is very low(1.25%). As time passed, the incidence of hypothyroidism increased, reaching 35% within 15 years. All cured patients had normal growth and produced offspring whose intelligence and development were normal. No one was diagnosed with thyroid carcinoma or leukemia in his/her medical follow-ups.ConclusionsUsing 131I for treating children and adolescents with Graves hyperthyroidism was effective and safe. The minimal side effects make it worthy of wide application in clinics.
Expression of pprM gene from Deinococcus radiodurans in eukaryotic cells
Shuya He, Qi Yang, Rujing Wang, Fangzhu Xiao, Wuzhou Wang, Yan Tang, Yuwei Jiang, Yun Ma
2017, 41(2): 103-107. doi: 10.3760/cma.j.issn.1673-4114.2017.02.005
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ObjectiveTo enhance the radiation resistance of eukaryotic cells and to identify the mechanisms that underlie radiation resistance, the radioresistant pprM gene was amplified from Deinococcus radiodurans and used to construct a recombinant pEGFP-C1-pprM plasmid for the expression of PprM protein in 293T cells.MethodsThe pprM gene was amplified from pGEX-6p-1-pprM via PCR and purified from agarose gel with a DNA recovery kit. The purified PCR product was digested with EcoR Ⅰ and BamH Ⅰ and ligated into the pEGFP-C1 plasmid. Recombinant plasmids were transfected into competent JM109 cells, which were then cultured on LB solid medium that contained kanamycin. Positive clones were identified and characterized via bacterial colony PCR, restriction enzyme digestion, and sequencing analysis. Lipofectamine 2000 reagent was used to transfect pEGFP-C1-pprM plasmids into 293T cells. Green fluorescent fusion protein was observed via fluorescence microscopy and identified by Western blot.ResultsBacterial colony PCR and double digestion showed that the target band is approximately 400 bp in length. Sequencing results showed that the base sequence was identical to the original gene sequence, thus indicating the successful construction of the recombinant plasmid. Fluorescence photography results showed that pEGFP-C1-pprM plasmids were successfully transfected into 293T cells. Western blot results showed that fusion protein is approximately 40×103 in weight.ConclusionsThe pEGFP-C1-pprM plasmid was transfected into 293T cells, which then successfully expressed PprM protein. This study provides the foundation for future research on the pprM gene and the effects of its products on the radiation resistance of 293T cells.
The influence of KGF on CTGF and Bcl-2 gene in duodenal tissue induced by radiation
Yayi Yuan, Yue Ren, Ruifeng Zhang, Hongyan Liu, Juancong Dong, Zhongxin Zhang, Yahui Zuo
2017, 41(2): 108-112. doi: 10.3760/cma.j.issn.1673-4114.2017.02.006
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ObjectiveTo observe the effects of keratinocyte growth factor(KGF) on connective tissue growth factor(CTGF) and B-cell lymphoma 2(Bcl-2) gene expressions in radiation-induced duodenal tissue, and to investigate the molecular mechanism of KGF in radiation-induced intestinal injuries.MethodsUsing the stochastic indicator method, Kunming mice were randomly divided into control, radiation, and treatment groups, each with 10 mice. The control group did not undergo the radiation process. The radiation group and treatment group underwent abdominal cavity irradiation with a dose rate of 0.678 Gy/min and an absorbed dose of 8 Gy with γ-ray. For 2 d before and 3 d after irradiation, KGF with a dose of 6 mg/kg was administered via intraperitoneal injection to the KGF treatment group. All mice were executed 15 d after irradiation, after which the duodenal tissue pathological slices were captured. Quantitative polymerase chain reaction was used to detect the KGF, CTGF, and Bcl-2 gene relative expressions in duodenal tissue. The measurement data were x±s. The two groups were compared using independent samples t-test, and P < 0.05 indicated that the difference was statistically significant.ResultsFor the control group, the duodenum intestinal villus and crypt structure were complete. For the radiation group, villi atrophy was shorter or fell off, and parts of the crypt and villi were observed in few apoptotic cells. For the treatment group, the organizational structure was complete, and a small amount of crypt can be seen in apoptotic cells. Compared with the control group, KGF, CTGF, and Bcl-2 gene expressions significantly increased after irradiation(t=-125.55, -6.55, -6.69, all P < 0.05). Compared with the radiation group, the gene expression of CTGF was significantly down-regulated(t=4.89, P < 0.05), and that of Bcl-2 was significantly up-regulated in the treatment group(t=-20.96, P < 0.05).ConclusionsThe model of acute radioactive duodenitis was successfully established. KGF repair damage was caused by ionizing radiation through down-regulating CTGF gene, and reduce apoptosis was caused by the regulation of the expression levels of the apoptosis-related Bcl-2 gene.
Effect and safety evaluation of 50-Hz 1-mT pulsed electromagnetic field on the immunomodulation of human umbilical cord mesenchymal stem cells
Fang Cao, Huanting Zhang, Liqing Du, Qiang Liu, Xiaocang Cao
2017, 41(2): 113-120. doi: 10.3760/cma.j.issn.1673-4114.2017.02.007
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ObjectiveTo investigate the effect of 50-Hz, 1-mT pulsed electromagnetic field (PEMF) on the immunomodulation of human umbilical cord mesenchymal stem cells(MSCs) and to evaluate the safety of PEMF as a therapeutic strategy.MethodsChanges in cell viability was observed via MTT. Real-time PCR was used to detect the expression levels of cyclooxygenase 2(COX2), indoleamine 2, 3-dioxygenase(IDO), IL-10, hepatocyte growth factor(HGF), and transforming growth factor-β(TGF-β) in MSCs. To explore the safety of PEMF, a flow cytometry experiment was conducted to observe apoptosis and reactive oxygen species(ROS) level. DNA damage was detected via comet assay. Data were statistically analyzed via t-test with SPSS 19.0. P < 0.05 was considered statistically significant.ResultsCell viability increased, with the most obvious increase in 4 h/d(t=3.505, P < 0.05). In interferon-γ(INF-γ)-activated MSC, the expression levels of immunomodulation factors improved after PEMF irradiation(t=2.436-3.747, all P < 0.05). Furthermore, PEMF did not induce cell apoptosis, ROS generation, and DNA damage.Conclusion50-Hz, 1-mT PEMF improves MSC immunomodulation and may not cause radiation injury.
Biological effects of radiation-induced exosomes
Chen Wang, Dexiao Yuan, Chunlin Shao
2017, 41(2): 121-125. doi: 10.3760/cma.j.issn.1673-4114.2017.02.008
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Exosomes are small extracellular vesicles released from normal and tumor cells. These vesicles contain proteins, lipids, and noncoding RNAs, and can mediate intercellular communication among different cell types in the body, thus affecting physiological and pathological processes. Emerging evidence indicates that radiation-induced exosomes facilitates the interaction between a tumor and its microenvironment. This article reviewed the biological effects of radiation-induced exosomes on tumor radiotherapy and discussed the role of such exosomes in tumor angiogenesis.
Advances in the treatment of differentiated thyroid cancer
Yuanqi Zhang, Deshan Zhao
2017, 41(2): 126-131. doi: 10.3760/cma.j.issn.1673-4114.2017.02.009
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Differentiated thyroid cancers(DTC) are generally considered low-risk malignant tumors. Radioiodine ablation following thyroidectomy and thyroid hormone suppression therapy are standard treatment in patients with metastatic DTC. Patients with DTC obtain many benefits from a three-step therapy schedule(i.e., thyroidectomy+radioiodine ablation+thyroid hormone). A proportion of patients with locally advanced or metastatic disease and poorly differentiated or dedifferentiated thyroid cancer become refractory to radioactive 131I therapy. After sensitizer and/or redifferentiation inducer treatment, thyroid cancer cells in patients with refractory thyroid cancer increase 131I uptake and the effects of 131I treatment are improved for patients with refractory thyroid cancer. The emergence of targeted drug treatment technology provides a broad prospect for thyroid cancer refractory to 131I therapy. Progress in the areas of sensitizers, redifferentiation inducers, and targeted drug treatment techniques for treating thyroid cancer refractory to 131I therapy is discussed in this review.
Application of radionuclide imaging on differential diagnosis of Parkinson disease
Weiwei Deng, Chunyin Zhang
2017, 41(2): 132-136. doi: 10.3760/cma.j.issn.1673-4114.2017.02.010
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The differential diagnosis of Parkinson disease can be challenging. Radionuclide imaging can provide the molecular and metabolic information so that it is helpful for differential diagnosis of Parkinson disease from atypical parkinsonism or other neurological disability such as essential tremor. The application of radionuclide imaging in the differential diagnosis of Parkinson disease was reviewed in this article.
REVIEW ARTICLE
Extraosseous findings on bone scintigraphy and research progress of its mechanism
Zhen Zou, Yani Chang, Zhifang Wu
2017, 41(2): 137-142, 155. doi: 10.3760/cma.j.issn.1673-4114.2017.02.011
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Chemisorption or ion exchange of 99Tcm-MDP on the surface of hydroxyapatite crystals can facilitate bone imaging, which can be used for the diagnosis of various bone disorders. However, extraosseous uptake in soft tissue structures on bone scans has been observed in some instances. Although the exact mechanism of its occurrence is currently unclear, most researchers have proposed that its mechanism include calcification of soft tissues(e.g., dystrophic calcification, and metastatic calcification), increased regional vascularity, technical artifacts, and radiopharmaceutical binding to macromolecules in the tissues. Identifying the specific mechanisms and detecting the occurrence of extraosseous uptake on the bone scan can facilitate the detection of disorders in other systems, thus reducing examinations and enhancing the diagnostic value of the study. The present essay reviews all the related articles and illustrates the commonly encountered extraosseous uptake and its possible mechanisms.
Clinical value and latest developments of coronary artery calcification scores and gated myocardial perfusion imaging in the diagnosis of coronary artery disease
Lubing Sun, Qiao Ruan
2017, 41(2): 143-149. doi: 10.3760/cma.j.issn.1673-4114.2017.02.012
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Myocardial perfusion imaging(MPI) plays an increasingly important role in the diagnosis, risk stratification, and prognosis of coronary heart disease, and coronary artery calcification scoring(CACS) can refine the risk stratification and prognosis of coronary heart disease. However, both methods possess limitations and deficiencies. The combination of CACS and MPI compensates for these deficiencies and provides detailed information to the physician. SPECT/CT generates CT images for attenuation correction when collecting MPI. CACS scans acquired during normal expiration can also be used for attenuation correction. The use of these scans not only reduces the radiological dose but also provides detailed information to the physician. This review focuses on the clinical values of CACS, MPI, and their combination and presents the latest developments in obtaining MPI and CACS images in one scan.
IQ·SPECT, Cadmium-Zinc-Telluride SPECT, and conventional SPECT application in myocardial perfusion imaging
Xiaoxiao Jin, Zhifang Wu, Guang Hu, Hua Wei
2017, 41(2): 150-155. doi: 10.3760/cma.j.issn.1673-4114.2017.02.013
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Cadmium-Zinc-Telluride(CZT) SPECT and IQ·SPECT are new technologies used in myocardial perfusion imaging and are important in the development of nuclear cardiology. These technologies exhibit higher sensitivity and spatial resolution, shorter acquisition time, and lower injection and radiation doses than conventional SPECT. In contrast to the conventional SPECT system equipped with standard low-energy high-resolution collimators, IQ·SPECT adopts SMART-ROOM collimators and cardiac-centric acquisition to improve detection sensitivity. The detectors of CZT SPECT consist of semiconductor materials, instead of conventional sodium iodide(NaI) crystals, to improve energy resolution, spatial resolution, sensitivity, and signal-to-noise ratio. These detectors can also quantitatively analyze myocardial flow reserve. This paper reviews the imaging principle, performance parameters, and clinical application of three SPECT systems.
2017, 41(2): 156-158. doi: 10.3760/cma.j.issn.1673-4114.2017.02.014
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