2020 Vol. 44, No. 5

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2020, 44(5): 0-0.
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2020, 44(5): 1-4.
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Invited Perspective
Tregs and radiation-induced lung injury
Liqing Du, Qiang Liu
2020, 44(5): 273-275. doi: 10.3760/cma.j.cn121381-202003039-00042
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As one of the common side effects of radiotherapy for thoracic tumor, radiation induced lung injury (RILI) might develop into radiation-induced pulmonary fibrosis several months later. A lot of exploration on the mechanisms of the occurrence and development of RILI was carried out in recent years. The immunological mechanisms of regulatory T cells (Tregs) in the progress of RILI have been paid more attention by domestic and foreign scholars. The key topic of the present issue published several articles on Tregs and RILI. These articles reported the results of Tregs involved in the occurrence and development of RILI from the aspects of the changes in the number of Tregs in lung tissue and immunological mechanisms, and which provided important scientific basis for the prevention and treatment of RILI.
Tregs and Radiation-Induced Lung Injury
Effect of Tregs differentiation on radiation-induced lung injury
Rui Wang, Wei Wei, Zhuo Dong, Zhiyuan Chen, Junxuan Yi, Yuxin Liu, Yulu Gu, Gang Zhao, Shunzi Jin
2020, 44(5): 276-285. doi: 10.3760/cma.j.cn121381-201903029-00027
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Objective To investigate the effects of the differentiation of regulatory T cells (Tregs) on radiation-induced lung injury and its mechanism. Methods A mouse model that inhibits Tregs was established. C57BL/6 mice were divided into the control group, simple irradiation group, irradiation+IgG group, and irradiation+CD25 group according to the random number table method. Each group comprised 12 mice. The mice in the simple irradiation group, irradiation+IgG group, and irradiation+CD25 group were given a single 20 Gy X-ray full chest irradiation. The mice in the irradiation+IgG group and irradiation+CD25 group were intraperitoneally injected with IgG antibody and CD25 antibody every week, respectively. Six mice were killed at 4 and 8 weeks after irradiation respectively. Flow cytometry was used to detect the percentage of CD25+Foxp3+Tregs in the lung tissue of each group of mice to identify whether the model was established successfully. Then, Western blot was used to detect the expression of neuropilin 1(NRP1) in the lungs of the mice in the control group and irradiation group. Immunofluorescence was used to detect the percentage of CD25+NRP1+Tregs. Photos were taken to observe the skin damage of each group of mice. Hematoxylin eosin staining was used to detect the pathological changes of lung tissue. The secretion of cytokines, namely, transforming growth factor-beta 1 (TGF-β1), interleukin (IL)-17A, interferon-γ (IFN-γ), IL-2, and IL-4, in the lung tissue of each group was detected by enzyme-linked immunosorbent assay. Independent sample t-test was used for comparison between the two groups. Results The results of flow cytometry showed that the percentage of CD25+Foxp3+Tregs ((1.73±0.04)%, (2.13±0.15)%) in the lung tissue of mice in the simple irradiation group was significantly higher than that in the control group ((1.14±0.02)%, (1.70±0.06)%) (t=−26.680, −4.545; P=0.000, 0.010) at 4 and 8 weeks. After the inhibition of Treg cells, the percentage of CD25+Foxp3+Tregs ((0.72±0.14)%, (0.27±0.02)%) in the lung tissue of mice in the irradiation+CD25 group was significantly lower than that in the irradiation group alone (t=5.296, 37.538; both P=0.000). The result of Western blot showed that the expression of NRP1 protein in the lung tissue of mice in the irradiation group increased significantly (t=−7.341, −9.127; both P=0.000). The results of immunofluorescence showed that the proportion of CD25+NRP1+Tregs in the lung tissue of mice in the irradiation group was higher than that in the control group at 4 and 8 weeks after irradiation. The proportion of CD25+NRP1+Tregs in the irradiation+CD25 group was lower than that in the irradiation group (t=8.926, 14.457; P=0.001, 0.000). The skin lesions observed were severe in the simple irradiation group. The skin in the irradiated+CD25 group was almost intact at 4 weeks, and hair removal and peeling still occurred at 8 weeks. Hematoxylin eosin staining showed that relative to that in the control group, the lung tissue structure of the mice in the irradiated group was destroyed, the alveolar wall was thickened, and the extracellular matrix was increased at 4 and 8 weeks after irradiation. The lung tissue of the irradiated+CD25 group was intact and the alveolar wall was slender. As indicated by the changes in inflammatory factors, relative to that in the control group, the secretion of IL-17A and IL-4 in the lung tissue of mice increased in the simple irradiation group (t=−8.492, −15.796; P=0.001, 0.000) at 4 weeks. After 8 weeks of irradiation, the levels of TGF-β1 and IL-17A increased significantly (t=−11.072, −7.167; P=0.000, 0.002), and the levels of IL-2 decreased at 4 and 8 weeks. IFN-γ secretion increased at 4 weeks (t=−27.393, P=0.000) and decreased at 8 weeks. Relative to that in the simple irradiation group, TGF-β1 and IL-17A decreased (t=6.037, 4.524, 5.496, 4.772; all P=0.000), IFN-γ increased (t=−7.006, −12.565; P=0.002, 0.000) at 4 and 8 weeks, and IL-2 and IL-4 decreased at 4 weeks and increased significantly at 8 weeks (t=2.866, −9.090, 8.833, −7.191; all P=0.000) in the irradiation+CD25 group. Conclusion The differentiation of Tregs occurs in the lung tissue of mice with radiation-induced lung injury and promotes the development of radiation-induced lung injury by secreting TGF-β1 pro-inflammatory factor while interfering with the balance of helper T cell (Th)1/Th2 type cytokines.
Early response of immune-related T cells in the lung tissue of mice exposed to gamma rays in the chest
Tingting Xi, Shuang Geng, Zewen Sun, Yilong Wang, Zhihua Yang, Xiujie Pan, Maoxiang Zhu
2020, 44(5): 286-290. doi: 10.3760/cma.j.cn121381-202003038-00025
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Objective To explore the early response of immune-related T cells in the lung tissue of mice, whose chests were exposed to gamma rays. Methods A total of 112 C57BL/6 mice (6–8 weeks old, (20 ± 2) g) were randomly divided into 14 groups (7 irradiation groups and 7 corresponding control groups, n = 8). The irradiation groups received a single dose of chest irradiation (20 Gy) by using a 60Co ray source. The immune cells in the lung, including white blood cells and T cell (CD3+) and its subtypes (CD4+/CD8+/Treg) in the lung tissue, were detected using flow cytometry at 3 h, 12 h, and 1, 2, 3, 7, and 14 days after irradiation. The t test was used to compare the two groups. Results The leukocytes in the lung tissue of irradiated mice were significantly reduced (t=3.446–7.781, all P<0.01). The CD3+ T cells decreased early after irradiation (3 h–2 days; t=4.413–15.430, all P<0.01). The Treg cells (CD4+CD25+Foxp3+) increased significantly (t=2.813–4.406, all P<0.05). The CD4+ T cells decreased significantly at the early stage after irradiation (3 h and 12 h; t=5.019, 4.912; both P<0.01) and returned to the control level after one day. The CD8+ T cells did not change at the early stage (3 h and 12 h), decreased significantly at 1 and 3 days ( t=6.736, 4.738; both P<0.01), and increased significantly after seven days (t=7.537, 3.903; both P<0.01). The CD4+/CD8+ ratio decreased within 12 h after irradiation ( t=5.624, 4..083; both P<0.01), increased significantly at 1 and 3 days (t=13.410, 5.702; both P<0.01), and decreased again after seven days (t=5.505, 3.928; both P<0.01). Conclusion Chest-irradiated mice showed different changes in immune-related cells in the lung tissue at the early stage after irradiation, which may be related to the damage of immune cells by radiation and the immune response produced by the body's stress response.
Clinical Investigations
Preliminary quantitative analysis of the distribution heterogeneity of lung ventilation/perfusion in patients with chronic thromboembolic pulmonary hypertension
Rongzheng Ma, Meng Wang, Wei Fang, Zongyao Zhang, Lei Wang
2020, 44(5): 291-297. doi: 10.3760/cma.j.cn121381-201902028-00021
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Objective To quantitatively assess the distribution heterogeneity of lung ventilation/perfusion (V/Q) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to evaluate the correlation between distribution heterogeneity parameters and pulmonary artery pressure. Methods Twenty CTEPH patients, comprising twelve males and eight females (age, 48.75±14.07 years old), who were hospitalized in Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from February 2018 to December 2018, were confirmed to have CTEPH by means of right heart catheterization and pulmonary angiography. Thirteen controls, comprising seven males and six females (age, 54.46±8.56 years old), were also enrolled. Patients and controls underwent V/Q san and low-dose CT, and echocardiography was performed within 1 week to estimate pulmonary artery systolic pressure (PASP). The heterogeneity indexes of lung V/Q distribution include LogSDV, LogSDQ, and LogSDVQR (V and Q and V/Q are the radioactivity count of ventilation and perfusionand, and its ratio). SD is the standard deviation. The abovementioned indexes were obtained by image reconstruction and analysis. Then, on CT images, the lung CT threshold was used to automatically delineate the boundary of the left lung, the right lung, and the whole lung as the volume of interest, and it was replicated on the pulmonary perfusion images to acquire the standardized uptake value (SUV), including peak of SUV (SUVpeak), maximum of SUV (SUVmax), minimum of SUV (SUVmin), mean of SUV (SUVmean), and standard deviation of SUV (SUVSD). SUVSD represents the heterogeneity of perfusion distribution. The comparation of two groups by utilising t-test. Using Pearson correlation to analyse distribution heterogeneity parameters and PASP correlation. Results The distribution of lung V/Q in the healthy control patients presented a symmetrical unimodal distribution, whereas the distribution curve of lung V/Q in patients with CTEPH presented an asymmetric multi-peak distribution. Compared with the control group, LogSDV, LogSDVQR, total pulmonary perfusion SUVpeak, SUVmax, and SUVSD significantly increased in the CTEPH group. The differences were statistically significant (LogSDV: 0.56±0.16 vs. 0.31±0.11, t=4.91, P=0.000; LogSDVQR: 0.61±0.15 vs. 0.40±0.14, t=3.89, P=0.001; SUVpeak: 19.12±7.94 vs. 10.81±4.05, t=3.48, P=0.002; SUVmax: 20.19±8.30 vs. 11.44±4.33, t=3.49, P=0.001; SUVSD: 3.54±1.44 vs. 2.42±0.91, t=2.50, P=0.018). The differences of LogSDQ, SUVmean, and SUVmin were not statistically significant between the two groups. PASP of CTEPH patients was (72.80±0.15) mmHg. The LogSDVQR was moderately correlated with PASP in patients with CTEPH (R=0.544, P=0.013). Conclusion The lung V/Q scan can quantitatively assess the distribution heterogeneity and reflect the pulmonary artery pressure status of the patients with CTEPH.
Effect of urinary iodine level on the 99Tcm-pertechnetate uptake function of the thyroid of patients with Graves' hyperthyroidism
Ke Chen, Yan Cui, Yaming Li
2020, 44(5): 298-302. doi: 10.3760/cma.j.cn121381-201903036-00035
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Objective To study the effect of urinary iodine level on the technicium (99Tcm)-pertechnetate uptake function of the thyroid of patients with Graves' hyperthyroidism. Methods One-hundred newly diagnosed patients with Graves' hyperthyroidism, including 20 males and 80 females (40.33±11.85 years old), from the First Affiliated Hospital of China Medical University from July to November 2018 were selected. Urinary iodine and creatinine concentrations were measured in urine samples from all patients, and patients were divided into low, medium, and high urinary iodine groups according to the standard of urinary iodine levels (≤100, 101−249, and ≥250 μg/gCr, respectively) and divided into seafood and no seafood intake groups according to whether the patients had eaten seafood 2 weeks before the examination. All patients underwent single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging to compute their thyroid-to-cervical soft tissue (T/C) ratio. Single-factor one-way analysis of variance was used for the comparison among groups, and least significant difference (LSD)-t test was used for the pairwise comparison among groups. Mann-Whitney U and t tests were used for comparison between two groups. Pearson test was used for correlation analysis. Results (1) The T/C ratios of patients with low, medium, and high urinary iodine levels were 24.18±8.43, 20.35±6.94, and 16.81±4.93, respectively, and the difference was statistically significant (F=5.40, P=0.006). The T/C ratios of the low and middle urinary iodine level groups were higher than that of the high urinary iodine level group with statistically significant differences (t=3.05, 2.38; P=0.003, 0.019), whereas the T/C ratios of the low and middle urinary iodine level groups were not statistically different. Urinary iodine level was negatively correlated with T/C ratio, and the difference was statistically significant (r=−0.24, P=0.023). (2) The levels of urinary iodine (M(P25, P75)) in the seafood and non-seafood groups were 229.2(163.06, 400.16) and 178.97(118.86, 245.54) μg/gCr, respectively, with statistically significant difference (Z=2.87, P=0.004). The T/C ratios of the two groups were 16.65±6.41 and 21.03±6.73, respectively, with statistically significant differences (t=3.10, P=0.003). Conclusion Elevated urinary iodine level in patients with Graves' hyperthyroidism remarkably inhibits the thyroid's 99Tcm-pertechnetate uptake function, and eating seafood before imaging increases the urinary iodine level in patients with Graves' hyperthyroidism.
Value of ultra-high b-value diffusion-weighted imaging combined with T2-weighted imaging in the diagnosis of peripheral prostate cancer
Jianping Liu, Xiaohong He, Yabin Jin, Shengqiang Lin, Mingyong Gao, Bin Li
2020, 44(5): 303-308. doi: 10.3760/cma.j.cn121381-201910023-00036
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Objective To investigate the clinical value of ultra-high b-value diffusion-weighted imaging (DWI) combined with T2-weighted imaging (T2WI) in the diagnosis of peripheral prostate cancer (PCa). Methods Forty-one patients who underwent ultrasound-guided prostate target puncture, clinicopathological diagnosis, and prostate MRI within one month before and after the puncture were selected from December 1, 2018 to October 1, 2019 in the First People's Hospital of Foshan. The patients' ages ranged from 49 to 89 years, with a median age of 69 years. All of the patients completed 3.0T ultra-high b-value DWI and T2WI fat suppression (2000 and 3000 s/mm2, respectively). With prostate target puncture pathology as the gold standard, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic (ROC) curve were calculated for the different imaging methods in PCa diagnosis. Results Among all the 41 patients, 26 had PCa (the 26 cases were peripheral zone PCa confirmed by clinical diagnosis and puncture site location) and 15 had benign hyperplasia. The sensitivity of T2WI, DWI (b=2000 s/mm2), DWI (b=3000 s/mm2), T2WI+DWI (b=2000 s/mm2), and T2WI+DWI (b=3000 s/mm2) in PCa diagnosis was 0.962 (25/26), 0.962 (25/26), 0.962 (25/26), 0.923 (24/26), and 0.923 (24/26) respectively; the specificity was 0.400 (6/15), 0.667 (10/15), 0.876 (13/15), 0.800 (12/15), and 1.000 (15/15), respectively; the accuracy was 0.756 (31/41), 0.854 (35/41), 0.926 (38/41), 0.878 (36/41), and 0.951 (39/41), respectively; and the area under the ROC curve was 0.681, 0.814, 0.914, 0.872, and 0.972(P=0.056, 0.001, <0.001, <0.001, <0.001), respectively. Conclusions DWI (b=3000 s/mm2) combined with the T2WI image exhibited high accuracy in PCa diagnosis. It is expected to become a highly reliable noninvasive examination procedure for the diagnosis of PCa.
High resolution CT features of pulmonary non-solid nodules for distinguishing minimally invasive adenocarcinoma from invasive adenocarcinoma
Xiangmeng Chen, Xiaobei Duan, Wansheng Long, Bao Feng, Jiayu Zhang, Lixia Sun, Ronggang Li, Guoqiang Tan, Chaotong Zhang, Xueguo Liu
2020, 44(5): 309-316. doi: 10.3760/cma.j.cn121381-201909041-00038
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Objective To explore the clinical application value of high resolution computed tomography (HRCT) features to differentiate pulmonary minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC) lesions appearing as non-solid nodules (NSNs). Methods A total of 187 patients (66 males and 121 females; aged 19–81 (54.8±12.2) years) with surgically and pathologically confirmed lung adenocarcinomas appearing as NSNs in HRCT images between February 2017 and April 2019 from the Affiliated Jiangmen Hospital of Sun Yat-sen University and the Fifth Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively. All patients were divided into MIA groups and IAC groups. The clinical characteristics of patients, including gender and age, were recorded. The HRCT features of NSNs, including nodule location, attenuation, size, sharpness, lobulated sign, spiculated sign, bubble lucency, air bronchogram sign, pleural traction, and para-nodule emphysema were reviewed and analyzed. The distribution difference of the clinical characteristics and HRCT features of NSNs was compared using univariate analysis between the MIA and IAC groups. Qualitative factors were analyzed using independent sample t-test or Mann-Whitney U test, whereas quantitative variables were analyzed using the χ2-test or Fisher exact test, as appropriate. The parameters with statistically significant difference were used for Logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was performed, and sensitivity, specificity, and accuracy were calculated. Results A total of 90 cases (25 males and 65 females; aged 25–76 (50.67±12.03) years) in the MIA group and 97 cases (41 males and 56 females; aged 19–81 (58.57±11.11) years) in the IAC group were identified. Significant statistical differences were observed in gender, age, nodule size, attenuation, sharpness, lobulated sign, spiculated sign, bubble lucency, air bronchogram sign, and pleural traction sign between the MIA and IAC groups ( χ2=4.292, P=0.038; Z=−4.577, P=0.000; Z=−8.467, P=0.000; t=−5.214, P=0.000; χ2=31.547, P=0.000; χ2=27.105, P=0.000; χ2=5.604, P=0.018; χ2=7.316, P=0.007; χ2=5.576, P=0.018; and χ2=4.989, P=0.026), respectively. Nodule size and attenuation were the independent risk factors for prediction of invasiveness degree of NSA, with odd ratio values of 1.428 (95% CI: 1.264–1.614; P=0.000) and 1.004 (95% CI: 1.001–1.008; P=0.006), respectively. The optimal cutoff value for nodule size and attenuation were 10.0 mm and −490 HU in the ROC curve analysis, with area under curve (AUC) values of 0.859 and 0.714, while the sensitivity, specificity, and accuracy were 75.3%, 83.3%, 79.1% and 56.7%, 77.8%, 66.8%, respectively. The combined model incorporated by nodule size and attenuation showed an AUC value of 0.867 and sensitivity, specificity, and accuracy of 78.9%, 82.5%, 80.2%, respectively. Conclusions HRCT features may be useful in distinguishing the invasiveness degree of pulmonary adenocarcinoma lesions manifested as NSNs. Nodule size and attenuation were the independent risk factors for the prediction of the invasiveness degree of pulmonary adenocarcinoma.
Review Articles
Research progress of PET molecular probes targeting Tau protein
Jianhua Jia, Yuqing Duan, Wenbin Hou, Yiliang Li
2020, 44(5): 317-322. doi: 10.3760/cma.j.cn121381-201910028-00031
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Abnormal accumulation of Tau protein, the primary indicator of Alzheimer(AD) and non-AD Tau-protein diseases, is closely associated with neurodegeneration and cognitive impairment. In recent years, several first-generation specific Tau-protein PET molecular probes, including 18F-THK5351, 18F-AV1451, and 11C-PBB3, have been developed and tested in clinical trials. Off-target binding is commonly used in first-generation PET molecular probes to promote the development of second-generation specific Tau-protein PET molecular probes with high binding affinity and selectivity. The potential of Tau-protein PET imaging as a biomarker in tauopathies and the latest progress in novel Tau molecular probes is reviewed in this study.
Advance in study of microRNA in occurrence and development of thyroid carcinoma
Xiaoyun Lin, Shasha Hou, Jian Tan
2020, 44(5): 323-327. doi: 10.3760/cma.j.cn121381-201904035-00034
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MicroRNAs (miRNAs) are endogenous, evolutionarily highly conserved noncoding single-stranded small RNAs. They play important roles in multiple biological and metabolic processes, including signal transduction, and cell proliferation, differentiation and apoptosis. MiRNAs can act as tumor suppressor genes or oncogenes, which are closely related to the formation of tumors. Recent studies have found that miRNA is closely related to thyroid cancer, and is involved in the occurrence and development of thyroid cancer, and is correlated with its highly invasive characteristics. In this paper the available data on miRNA deregulation in different thyroid tumors and the putative role of miRNA in thyroid cancer development were reviewed.
Research progress on the relationship between homocysteine and thyroid diseases
Ruirui Qin, Yali Cui, Jianhua Jin
2020, 44(5): 328-332. doi: 10.3760/cma.j.cn121381-201901011-00018
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Homocysteine (Hcy) is an intermediate product of methionine metabolism and exists in blood in various forms. The pathogenic effect of Hcy in hypertension, immune system, tumor, cardiovascular, and cerebrovascular diseases has been proven since the 1930s. The relationship between Hcy and thyroid diseases has attracted considerable attention from researchers in recent years due to its high correlation with the occurrence and development of various thyroid diseases. The author reviews the research progress of the relationship between Hcy and related thyroid diseases, such as hyperthyroidism, hypothyroidism, chronic lymphocytic thyroiditis, and thyroid cancer.
Case Reports
Appearance of a solitary Rosai-Dorfman disease of tibia on 18F-FDG PET/CT: A case report and literature review
Jianjie Wang, Luna Ma, Zhiyong Tian, Yiwen Chen, Xue Liu, Chaoyu Pu
2020, 44(5): 333-336. doi: 10.3760/cma.j.cn121381-201905008-00026
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Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare histiocytic disease. Typically, a patient with RDD presents with painless bilateral cervical lymphadenopathy. The involvement of extranodal organs, such as the skin, upper respiratory tract, and bone, may also occur. Bone involvement occurs in approximately 8% of patients with RDD. Obtaining an affirmatory diagnosis by non-specific radiological findings is difficult. The final diagnosis can be achieved by biopsy and pathological examination of the lesion. The 18F-FDG PET/CT results of a young patient aged 36 with RDD who presented with intermittent pain in the right leg was reported in this article. This case illustrates the usefulness of functional fused modality in differentiating diagnosis and in identifying the extent of this disease and the appropriate sites for biopsy.
A case of primary systemic amyloidosis with cardio-kidney damages: the whole body soft tissue 99Tcm-MDP imaging
Haijun Wang, Rong Wang, Yongle Wang, Lizhen Yang
2020, 44(5): 337-339. doi: 10.3760/cma.j.cn121381-201904031-00013
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The author reports a case of primary systemic amyloidosis with cardio-kidney damages, the whole body soft tissue uptake 99Tcm-MDP. Based on clinical symptoms, signs, laboratory tests and imaging examinations, the patients were diagnosed with primary systemic amyloidosis. When the whole body soft tissue extensive and symmetrical uptake the radiopharmaceutical in bone scanning, amyloidosis should be highly suspected, and suggesting further clinical examination.