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Expanding the application and research of PET molecular imaging in neuroscience
Jun Zhao
2019, 43(6): 493-495. doi: 10.3760/cma.j.issn.1673-4114.2019.06.001
Application of nanotechnology for diagnosis of Alzheimer's disease
Kai Zhang, Kexin Shi, Chentao Jin, Mei Tian, Mingrong Zhang, Hong Zhang
2019, 43(6): 496-502. doi: 10.3760/cma.j.issn.1673-4114.2019.06.002
Alzheimer's disease (AD) is a common neurodegenerative disorder, which is clinically characterized by progressive cognitive deficit and memory impairment. It seriously affects mental health, physical activity, and quality of life of patients in the late stage. However, early diagnosis of AD remains one of the greatest challenges worldwide. Extracellular amyloid-β (Aβ) plaques composed of Aβ and intraneuronal neurofibrillary tangles consisting of hyperphosphorylated Tau proteins are considered as the key pathological hallmarks of AD. Detection of Aβ and Tau protein is considered critical for the early diagnosis of AD. In recent decades, nanotechnology has developed rapidly, and nanotechnology-based Aβ- or Tau-targeted detection has provided the possibility for the early diagnosis of AD. The present review focuses on the research of nanotechnology in the diagnosis of AD.
PET molecular imaging of neuroinflammation in Alzheimer's disease
Yan Zhong, Chentao Jin, Mingrong Zhang, Hong Zhang
2019, 43(6): 503-509. doi: 10.3760/cma.j.issn.1673-4114.2019.06.003
Alzheimer's disease (AD) is a common neurodegenerative disease, but its underlying pathogenesis remains ambiguous. Emerging evidence suggests that neuroinflammation plays a crucial role in the pathogenesis of AD. As an advanced imaging technique for clinical applications, PET molecular imaging permits the non-invasive visualization of in vivo neuroinflammatory processes in AD. This review provides an overview of the molecular basis of neuroinflammation in AD and summarizes recent progress in PET molecular imaging of neuroinflammation.
Advances in imaging studies of hippocampus in patients with mild cognitive impairment
Yifan Chen, Chunlei Cui, Yusheng Su, Zhigang Liang
2019, 43(6): 510-517. doi: 10.3760/cma.j.issn.1673-4114.2019.06.004
The hippocampus is an important brain region related to learning and memory. MRI, PET and other imaging methods can provide structural, functional and glucose metabolism indicators of the hippocampus, and provide more imaging support for early screening and diagnosis of mild cognitive impairment (MCI). This paper mainly reviews the imaging research progress of hippocampal volume, hippocampal functional connectivity and hippocampal glucose metabolism in patients with amnestic MCI, with a view to finding more sensitive imaging indicators for the diagnosis of MCI.
Application of PET/CT in depression and related research advances
Xuerong Li, Lihong Bu
2019, 43(6): 518-522. doi: 10.3760/cma.j.issn.1673-4114.2016.06.005
Depression is a common mood disorder, which seriously affects the quality of life of patients. Accurate diagnosis and timely treatment are important. However, the pathogenesis of depression is incomplete clear, and there is also a lack of specific examination methods are lacking. Conventional examinations face various technical bottlenecks in the diagnosis and treatment effect of depression. However, molecular imaging research provides new research ideas and methods for depression. The author reviews the research progress of PET/CT in term of neuronal mechanism, diagnosis and detection of depression.
PET receptor imaging on neurofunctional changes in obesity
Kexin Shi, Xiaohui Zhang, Chentao Jin, Mei Tian
2019, 43(6): 523-527. doi: 10.3760/cma.j.issn.1673-4114.2019.06.006
Obesity prevalence increases worldwide, and the risk of various correlated diseases consistently grows. Although alterations in brain structure and regional activation pattern of obese individuals were widely explored in MRI and functional MRI studies, they remain incompletely understood at the molecular level. Receptor imaging with PET has been applied in obesity studies given its in vivo access to reveal brain receptor functional alterations. This article provides an overview on the role of PET brain receptor imaging in obesity.
Efficiacy of 131I-generation 5.0 polyamidamine-mediated targeting peptide in the mice with medullary thyroid carcinoma
Chengtao Feng, Haibo Zhang, Hao Zheng, Ziyan Wang, Yun Deng, Jihua Zhao, Gaohong Zhu
2019, 43(6): 528-537. doi: 10.3760/cma.j.issn.1673-4114.2019.06.007
Objective To synthesize the novel targeting probes 131I-generation 5.0 polyamidamine (PAMAM(G5.0))-SR (where SR: Ser-Arg-Glu-Ser-Pro-His-Pro), 131I-PAMAM(G5.0)-GP (where GP: Gly-Pro-Leu-Pro-Leu-Arg), and 131I-PAMAM(G5.0)-SR/GP (double targeting peptides) as experimental groups and evaluate their target capability toward medullary thyroid carcinoma (MTC). Methods The target peptides SR, GP, and SR/GP were purified and analyzed by using high-performance liquid chromatography and then covalently linked with the modified PAMAM(G5.0) to synthesize PAMAM(G5.0) peptides [PAMAM(G5.0)-SR, PAMAM(G5.0)-GP, and PAMAM(G5.0)-SR/GP]. The diameter and zeta potential of PAMAM(G5.0) alone and PAMAM(G5.0) peptides were detected by using dynamic light scattering. The modified PAMAM(G5.0) and PAMAM(G5.0) peptides were labeled with radioisotope 131I using the chloramine T method. The radiolabeling rate, radiochemistry purity, and stability were determined by using thin-layer chromatography. SPECT/CT imaging was performed in all groups at 4, 8, 12, 24, and 48 h after the probes were injected into the peritoneal cavity of the model mice. The ratio of target to non-target (T/NT) was then detected. The percentage injection dose per gram (%ID/g) with the tumor and important organs of the model mice were calculated. One-way analysis was used to compare the T/NT in different groups at the same time, T/NT in same group at the different time, %ID/g at 24 h in different groups. LSD-t test was used to compare date between two groups. Results The purity of purified PAMAM(G5.0)-SR, -GP, and -SR/GP were at 99%. The diameter of PAMAM(G5.0), PAMAM(G5.0)-SR, PAMAM(G5.0)-GP, PAMAM(G5.0)-SR/GP were 4.47, 5.70, 4.71, 5.95 nm, and zeta potentials were +37.95, +20.02, +28.34, +24.37 mV respectively. The radiolabeling rates of the four types of 131I probes were above 75%. The radiochemistry purities of the purified probes were more than 90% and remained over 85% after 48 h incubation at room temperature. All the T/NT of the experimental groups were higher than those of the control groups. The T/NT significantly increased in 131I-PAMAM(G5.0)-GP (6.03±1.45) at 4 h (t=3.235, P=0.033; t=3.843, P=0.019) compared with those in the positive and negative control groups (2.18±0.39 and 1.36±0.00, respectively). The T/NT significantly increased in 131I-PAMAM(G5.0)-SR (5.12±1.65, 4.82±0.09, and 3.41±1.01) at 8, 12, and 24 h (t=4.004, P=0.017; t=3.388, P=0.027; t=4.180, P=0.009, respectively) compared with that in the negative control group (1.50±0.00, 1.43±0.65, and 1.34±0.81). The T/NT of 131I-PAMAM(G5.0)-SR (3.41±1.01) was significantly higher than that of 131I-PAMAM(G5.0)-GP (2.10±0.67) at 24 h post-injection (t=3.990, P=0.016). The tumor %ID/g in 131I-PAMAM(G5.0)-SR (1.80±0.18) was higher than that in other groups at 24 h, but no significant differences were observed (F=3.366, P=0.059). The peak values of the T/NT and ID%/g of the tumor were observed at 4 h in the 131I-PAMAM(G5.0)-GP and 131I-PAMAM(G5.0)-SR/GP groups and at 8 h in the 131I-PAMAM(G5.0) and 131I-PAMAM(G5.0)-SR groups. The T/NT value decreased to 57% from 4 h to 12 h in 131I-PAMAM(G5.0)-GP group. Conclusions The SR and GP peptides enhanced the targetability of 131I-PAMAMM (G5.0) on MTC cells and neovascularization. The 131I-PAMAM(G5.0)-GP probe may be suitable for diagnosis because of its rapid ingestion and excretion than other probes in the model mice. The 131I-PAMAM(G5.0)-SR probe may provide a new precision method for MTC treatment and follow-up because of its better targetability and longer residence time than other probes in the model mice.
Preliminary study of 131I-Tyr-Nivolumab for PD-1-related theranostics of colon cancer
Danni Li, Shengnan Ren, Weiwei Su, Ye Peng, Xiao Li, Changjing Zuo
2019, 43(6): 538-543. doi: 10.3760/cma.j.issn.1673-4114.2019.06.008
Objective We synthesized theranostic agent 131I-Tyr-Nivolumab, which targets programmed cell death-1 (PD-1), and studied its preliminary application in the mouse model with orthotopic colon cancer and high PD-1 expression. Methods 131I-Tyr-Nivolumab was prepared through indirect labeling, and the radiochemical purity and stability of products were evaluated. Ten mice with high expression of PD-1 colon neoplasm in situ were randomly categorized into the treatment and untreated groups. In the treatment group, 131I-Tyr-Nivolumab (11.1 MBq/10 μg) was injected into the tail vein, and SPECT/CT was then performed to observe the distribution of the theranostic agent in mice at different time points (2, 4, 24, and 65 h) after injection. After 5 days of treatment, the expression of Bax and Bcl-2 proteins in tumor tissues were quantified by immunohistochemistry. Results 131I-Tyr-Nivolumab had radiochemical purity greater than 99% and in vitro stability greater than 90% for 24 h. The theranostic agent was mainly distributed in the heart, liver, and intestinal tumors, and was eliminated by renal metabolism, and its uptake by the tumor tissue increased gradually at 2 h post-injection. The liver was visualized at 4 h post-injection, and the suspected tumor area of the intestine was clear at 24 h post-injection. Liver non-specific uptake was almost eliminated at 65 h post-injection. The ratios of radioactivity counts in the intestinal suspected tumor area to the whole-body radioactivity counts at 4, 24, and 65 h post-administration were (2.8±0.3)%, (8.4±0.2)%, and (1.8±0.5)%, respectively. The treatment group had significantly higher expression rate of Bax protein [(22.23±1.61)% vs. (13.64±2.43)%, t=−5.476, P=0.006] bur significantly lower expression rate of Bcl-2 protein [(13.81±4.64)% vs. (25.57±2.33)%, t=3.902, P=0.017] compared with the untreated group. Conclusion 131I-Tyr-Nivolumab targeting PD-1 was successfully synthesized and can be used as a theranostic agent for SPECT imaging and internal irradiation therapy. This method could provide a new idea for the theranostics of colon cancer.
Effects of melatonin on the radiosensitivity of human colon cancer cells
Qin Wang, Chang Xu, Liqing Du, Yan Wang, Yang Liu, Qiang Liu
2019, 43(6): 544-551. doi: 10.3760/cma.j.issn.1673-4114.2019.06.009
Objective To detect the effects of melatonin combined with γ-ray ionizing radiation on the proliferation of human colon cancer HCT 116 cells in vitro and in vivo and to explore the role of melatonin in regulating the radiosensitivity of HCT 116 cells. Methods The cohorts were divided into blank control group (HCT 116 cells were not given any treatment), melatonin group (HCT 116 cells were treated with 1 mmol/L melatonin for 2 h), radiation group (HCT 116 cells were exposed to 6 Gy γ-ray radiation), and melatonin+radiation group (HCT 116 cells were treated with 1 mmol/L melatonin for 2 h and then exposed to 6 Gy γ-ray radiation). In in vitro experiments, colony formation assay was used to detect cell proliferation after exposure to 0, 2, 4, 6, or 8 Gy radiation. Flow cytometry was applied to detect the cell cycle distribution at 24 h and cell apoptosis at 24 and 48 h after exposure to 6 Gy radiation. Comet assay was performed to detect DNA damage to cells 2 h after exposure to 6 Gy radiation. In in vivo experiments, the tumor-bearing nude mouse model was built by inoculating HCT 116 cells. The volume and inhibition ratio of tumor xenografts were examined. T-test was used for comparison between groups. Results ① In in vitro experiments, the colony number of HCT 116 cells treated with melatonin prior to radiation was significantly less than that of control cells (t=3.83, P=0.005). HCT 116 cells that were arrested at the G2 phase in the melatonin+radiation group (53.04%±4.67%) were increased, and significant differences were noted between the melatonin+radiation group and the radiation or melatonin group (t=2.940 and 20.660, P=0.017 and P<0.01, respectively). The cell apoptosis rate of HCT 116 cells in the melatonin+radiation group at 24 and 48 h after treatment was increased and reached (12.15±0.41)% and (30.57±1.91)%, respectively, which were markedly higher than those of the radiation (9.00%±0.70%, 8.69%±0.71%) or melatonin group (3.03%±0.42%, 12.56%±0.89%) (t=7.46, 17.75, 29.12, and 14.80, all P<0.01). The value of tail DNA, tail length, tail moment, and Olive tail moment in HCT 116 cells in the melatonin+radiation group were significantly higher than that in the radiation (t=4.72, 4.16, 4.74, 4.50, all P<0.01) or melatonin group (t=20.27, 22.80, 13.81, and 18.85, all P<0.01). ② In in vivo experiments, tumor xenografts in nude mice of the melatonin+radiation group grew slowly. The volume of tumor xenografts in the melatonin+radiation group at day 15 was significantly decreased compared with that in the radiation or melatonin group (t=3.51 and 2.72, P=0.006 and P=0.021, respectively). The inhibition ratio of xenografts in the melatonin+radiation group (54.7%±8.0%) was significantly higher than that in the radiation or melatonin group (t=7.50, 4.12, all P<0.01). Conclusion Melatonin combined with γ-ray radiation had obvious inhibition effect on colon cancer cells and increased the radiosensitivity of colon cancer cells.
Diagnostic accuracy of different types of computed tomographic angiography and magnetic resonance angiography for intracranial aneurysm: a Meta-analysis
Daoying Wang, Haiyang Li, Haijun Wang, Xinghui Li, Jinhui Tian
2019, 43(6): 552-560. doi: 10.3760/cma.j.issn.1673-4114.2019.06.010
Objective To perform a Meta-analysis to systematically review the accuracy different types of computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) for intracranial aneurysm (IAN). Methods PubMed, EMbase, Cochralle library, Cnki, China biomedical literature database, weipu, wanfang and other databases were searched to collect Chinese and English literatures on IAN diagnosis by different types of CTA and MRA before January 2018.The references were evaluated and screened according to the criteria of diagnostic research. In addition, quality assessment was conducted according to the Quality Assessment of Diagnostic Accuracy Studies 2, RevMan 5.3 and Metadisc 1.4 software was used to respectively compare the summary sensitivity (SEN), summary specificity (SPE), diagnostic odds ratio (DOR), summary positive likelihood ratio (PLR), summary negative likelihood ratio (NLR), pre-test probability, post-test probability between CTA, MRA and subgroup. The forest figure and a summary of receiver operating characteristic curve (SROC) was drawn out and the area under curve (AUC) was calculated. Deek's funnel plot was drawn by Stata 12.0 statistical analysis software to evaluate the publication bias of included literature. Heterogeneity was analyzed by Q test and I2. P<0.05 indicated that the difference was statistically significant. Results A total of 1754 records was retrieved and 38 studies involving 5212 patients were included. The results of meta-analysis showed that: ① The summary SEN, summary SPE, DOR, summary PLR, summary NLR, AUC, pre-test probability, post-test probability of CTA were: 0.947 (95%CI: 0.926, 0.963), 0.916 (95%CI: 0.864, 0.949), 195.328 (95%CI: 97.367, 391.847), 11.218 (95%CI: 6.861, 18.341), 0.057 (95%CI: 0.040, 0.082), 0.98 (95%CI: 0.96, 0.99), 20% and 74%; ② The summary SEN, summary SPE, DOR, summary PLR, summary NLR, AUC, pre-test probability, post-test probability of MRA were: 0.935 (95%CI: 0.899, 0.958), 0.956 (95%CI: 0.917, 0.977), 311.421 (95%CI:126.935, 764.038), 21.285 (95%CI: 11.114, 40.766), 0.068 (95%CI: 0.044, 0.107), 0.98 (95%CI: 0.97, 0.99), 20% and 84%; ③ The results of subgroup analysis showed that: there were no statistical difference between the different types of CTA and MRA in SROC. Conclusions The different types of CTA and MRA can be used to diagnose IAN, and the diagnostic accuracy is relatively high and basically consistent. Both CTA and MRA can be used as the first choice for diagnosing IAN.
Research Progress on Mechanism of skin damage and injury induced by solar radiation
Hongyan Li, Deguan Li
2019, 43(6): 561-568. doi: 10.3760/cma.j.issn.1673-4114.2019.06.011
In recent years, the incidence of skin cancer, especially squamous cell carcinoma, has increased significantly. About 90% of skin cancers are associated with ultraviolet radiation damage. Upon exposure of the skin to ultraviolet rays, especially UVB (290–320 nm) and UVA (320–400 nm), epidermal melanocytes migrate to adjacent keratinocytes by synthesizing melanin, thus providing light protection for the skin. A series of damage reactions, including tanning and inflammation, cell DNA damage, and photocarcinogenesis, occurred after the skin was stimulated by excessive ultraviolet radiation. Recent studies have found that visible light (400–700 nm) and ozone can also cause skin damage. The skin damage caused by environmental exposure is mainly attributed to the production of reactive oxygen species, which cause oxidative damage to protein, lipid, and nucleic acid, followed by a series of complex reactions within the skin. Damaged skin cells cause inflammatory reactions, resulting in ultimate damage to the skin. Therefore, understanding the mechanism of photoinduced skin damage and developing correct radiation protection measures are important for the treatment and prevention of related diseases. This review summarizes the effects of sunlight, including ultraviolet, visible, and ozone on skin damage, as well as the research on gene loci of suntan caused by sunlight, to explore new ways to prevent and treat skin damage caused by solar radiation.
Research progress in accurate targeted therapy for radioiodine refractory differentiated thyroid cancer
Xinxia Wang, Tengchuang Ma, Yali Cui
2019, 43(6): 569-575. doi: 10.3760/cma.j.issn.1673-4114.2019.06.012
The incidence of thyroid cancer is increases year by year. Traditional treatment for radioiodine refractory differentiated thyroid cancer is limited.Targeted therapy is a popular new treatment method in recent years, and has achieved positive results in the treatment of thyroid carcinoma. This article reviews the accurate targeting therapy strategy of radioiodine refractory differentiated thyroid carcinoma, drug targeting therapy, peptide receptor radionuclide targeting therapy, local precise therapy and immunotherapy.
The progresses in PET molecular imaging in the detection of epidermal growth factor receptor mutations in non-small cell lung cancer
Simin Wu, Rui Zhou, Shuang Wu, Mei Tian
2019, 43(6): 576-581. doi: 10.3760/cma.j.issn.1673-4114.2019.06.013
Lung cancer is one of the most common types of malignancy. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. Epidermal growth factor receptor (EGFR) targeted therapy can significantly improve the prognosis of patients with advanced NSCLC. In this case, determining EGFR mutation status is critical in selecting an optimal treatment regimen for these patients. However, the acquisition of good-quality tumor tissues for genetic alteration analysis remains a challenge for patients who cannot bear surgery and biopsy. Therefore, noninvasive in vivo diagnosis of EGFR mutation status in NSCLC patients is critical for patient management. Positron emission tomography (PET) with specific probe targeted to EGFR has the potential to fulfill this requirement. This study provides a brief review of the value of PET with multiple tracers in predicting the status of EGFR mutation.
Malignant inflammatory myofibroblastoma: 18F-FDG PET/CT imaging
Qian Zhang, Chao Ma, Zhongwei Lyu
2019, 43(6): 582-584. doi: 10.3760/cma.j.issn.1673-4114.2019.06.014
A case of malignant inflammatory myofibroblastoma was reported. The characteristics of the disease were analyzed using clinical symptoms, CT, 18F-FDG PET/CT examination, clinical diagnosis, pathological diagnosis, and prognosis. The understanding of this disease was deepened through literature review. The case was verified as malignant inflammatory myofibroblastoma. The disease progresses quickly and had low specificity. Diagnosis needed pathology and prognosis. Myofibroblastoma is mostly benign, and the incidence of malignant diseases is small. Once myofibroblastoma occurs, it is easy to misdiagnose. Thus, a combination of clinical, imaging, pathological, therapeutic, and prognostic considerations is needed.
Intracranial anaplastic hemangiopericytoma with bone metastasis: a case report
Lili Yuan, Jian Tan, Dekun Wu, Yandong Zhu, Yali Zhu, Chengming Huang
2019, 43(6): 585-588. doi: 10.3760/cma.j.issn.1673-4114.2019.06.015
A case of bone metastase secondary to intracranial anaplastic hemangiopericytoma (AHPC) was reported. The characteristics of the disease were analyzed on the basis of clinical symptoms and imaging examinations, especially bone imaging examination and pathology. The understanding of intracranial AHPC bone metastasis was deepened by literature review. Bone metastases are common in most malignant tumors, but intracranial AHPC, which is a rare central nervous system tumor, has an extremely low bone metastasis potential. In the present case, the multiple lesions of bone metastasis from intracranial AHPC were detected through a whole body bone imaging examination. Thus, whole body bone scans should be regarded as important examination tools for patients with malignant tumors during follow-up, especially patients with rare bone metastasis, because the scans have a key value in early detection, clinical staging, and treatment decision.
Graves' hyperthyroidism complicated with coronary heart disease treated by percutaneous coronary intervention under the guidance of myocardial perfusion imaging: a case report
Jianping Zhang, Xuehui Liu, Hongxu Yu, Na Liu, Hui Shen, Bing Chen
2019, 43(6): 589-592. doi: 10.3760/cma.j.issn.1673-4114.2019.06.016
A patient hospitalized with palpitation, chest tightness, and shortness of breath was reported in this study. She was definitively diagnosed with Graves' hyperthyroidism and had several risk factors of coronary heart disease (CHD), including old age, hypertension, diabetes, and hyperlipidemia. Resting and ATP stressing myocardial perfusion imaging were applied in 2 days to determine whether CHD exists in this patient. Results confirmed that the patient has extensive myocardial ischemia and a high risk of cardiac adverse events. Thus, coronary angiography was suggested. Revascularization was achieved after percutaneouscoronary intervention, and no hyperthyroidism crisis occurred. MPI is recommended for patients with hyperthyroidism and suspected CHD after excluding correlative contraindications to facilitate the risk stratification of CHD and guide further treatment strategies.