2015 Vol. 39, No. 3

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Original Article
Pharmacokinetics and tissue distribution of interferon α2b(Pseudomonas putida) administered via atomization inhalation and intramuscular injection by 125I labeling
Cuihong Yang, Jinjian Liu, Liping Chu, Honglin Gao, Liyun Zheng, Chongyuan Zhang, Licheng Liu, Yumin Zhang
2015, 39(3): 191-196. doi: 10.3760/cma.j.issn.1673-4114.2015.03.001
Abstract:
Objective To compare the in vivo pharmacokinetics and tissue distribution difference of interferon α2b(IFNα2b, Pseudomonas putida) in rabbits administered via atomization inhalation and intramuscular injection. Methods IFNα2b was radiolabeled with iodine-125 and then administered to rabbits at a dose of 450 000 IU/kg body weight(according to the recommended dosage for humans of 150 000 IU/kg body weight)via atomization inhalation and intramuscular injection. The pharmacokinetics of IFNα2b in rabbits was studied using radioisotope tracer technique. The distribution of IFNα2b in different tissues and the different parts of the lung at 0.5, 2, 4, 8, and 12 h was detected by ex vivo imaging and γ-counting methods. Results The pharmacokinetic results showed that the area under the curve, mean retention time, clearance, and half-life time of intramuscular injection group were (39.20 ± 1.89) ng·h-1·ml-1, (6.90± 0.21) h, (0.09±0.004) ml·kg-1·h-1, and (7.30±0.38) h, respectively, and the corresponding data of atomization inhalation group were (45.10±4.65) ng·h-1·ml-1, (16.10±1.37) h, (0.06 ± 0.010) ml·kg-1·h-1, and(12.10±1.19) h, respectively. The tissue distribution results indicated that the IFNα2b administered via atomization inhalation was mainly distributed in the lung, with the detectable radioactive signal as long as 12 h. However, high radioactive signals were observed in the kidney in the intramuscular injection group at 2 h, and then the signals gradually diminished. Conclusions Compared with the conventional intramuscular injection, atomization inhalation could evidently prolong the in vivo residence time of IFNα2b and exhibited higher lung accumulation. Consequently, the atomization inhalation of IFNα2b may have better therapeutic effect and longer duration of drug action for pulmonary viral and respiratory tract infections.
The value of gastric mucosa SPECT in the study of midgastric transverse band
Ming Chen, Chun Liu, Xiang Yan, Shixiong Liu
2015, 39(3): 197-200. doi: 10.3760/cma.j.issn.1673-4114.2015.03.002
Abstract:
Objective To investigate the value of SPECT gastric mucosa imaging in the study of midgastric transverse band(MTB). Methods SPECT gastric mucosa and gastric emptying imaging were performed in 45 healthy adults, and the image area and count/pixel ratio were statistically analyzed. Results Significant differences were found between proximal and MTB, distal and MTB, whole stomach and proximal, whole stomach and distal count/pixel ratio. MTB was also observed in gastric mucosa imaging, and the MTB in gastric mucosa imaging indicated the same clinical significance as that of the MTB in gastric emptying. Conclusions Gastric mucosa imaging can be used for qualitative determination, and alterations in the distribution of radionuclide indirectly reflect the changes in the gastric mucosal cells. MTB is a region that lacks gastric mucous cells; thus, this region is relatively weak in gastric receptivity dynamics.
Diagnostic efficacy of SPECT/CT fusion imaging in assessing possible bone metastases
Xuehui Liu, Hongjun Li, Hongxu Yu
2015, 39(3): 201-204. doi: 10.3760/cma.j.issn.1673-4114.2015.03.003
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Objective To evaluate the diagnostic efficacy of single photon emission computed tomography/computed tomography(SPECT/CT) in assessing possible bone metastases. Methods Sixty-four patients with history of primary cancer with 96 lesions that could not be definitively diagnosed using planar scintigraphy were included in this study, and SPECT/CT was performed. SPECT, CT, and SPECT/CT images were independently interpreted and scored by two experienced nuclear medicine physicians. The final diagnosis was confirmed by the pathological results or follow-up(≥6 months). The value of additional fused images was assessed using receiver operating characteristic(ROC) analysis. Results The sensitivity, specificity, accuracy, and negative and positive predictive values for SPECT/CT imaging were 93.1%, 86.8%, 90.6%, 91.5%, and 89.2%, respectively. The areas under the ROC curve were 0.956, 0.897, and 0710 for SPECT/CT-fused images, CT images, and SPECT, respectively. Conclusion SPECT/CT fusion imaging was more accurate and valuable compared with separate sets of SPECT and CT images.
Identification of 13N-NH3 and analysis of its radiochemical purity using high performance liquid chromatography-ultraviolet-flow-count
Shanzhen He, Shuxia Wang, Shilei Li, Peng Wang
2015, 39(3): 205-208. doi: 10.3760/cma.j.issn.1673-4114.2015.03.004
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Objective To establish a new, rapid, and effective method to identify 13N-NH3 and analyze its radiochemical purity. Methods The chromatographic method of high performance liquid chromatography-ultraviolet(HPLC-UV)-flow-count was performed using a C18 column with mobile phase of acetonitrile and 5 mmol/L sodium 1-octanesulfonate solution(V/V=1/3)at a flow rate of 0.5 ml/min and a wavelength of 210 nm. 15% 13N-NH3 and 0.1 mg/ml NaNO3 were detected separately, and their retention times were compared and identified. Results The UV retention times of NH3 and NaNO3 were 2.3 and 1.4 min, respectively, and the retention times of 13N-NH3 and 13N-NOx- were 5.8 and 3.1 min, respectively. The established separation method using HPLC-UV-flow-count showed good efficiency. Conclusion HPLC-UV-flow-count is a simple, valid, and rapid method to identify 13N-NH3 and analyze its radiochemical purity.
Evaluation of combined coronary CT angiography and dual-energy myocardial perfusion imaging for detection of acute myocardial infarction via second-generation dual-source CT: an experimental study in a porcine phantom model
Kai Sun, Kuncheng Li, Ruijuan Han, Shuancheng Bai, Junyan Wang, Yidong Qian, Zhihui Liu
2015, 39(3): 209-215. doi: 10.3760/cma.j.issn.1673-4114.2015.03.005
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Objective To evaluate the diagnostic accuracy of dual-energy "one-step"combined CT coronary angiography(CCTA) and myocardial perfusion imaging(MPI) for the detection of acute myocardial infarction via second-generation dual-source CT compared with histopathological and conventional coronary angiography(CAG) findings in a porcine phantom. Methods Seven minipigs underwent transcatheter embolization of the coronary arteries by using gelatin sponge to produce acute myocardial infarction. CAG, dual-energy CCTA, and MPI were performed 20 min before, immediately after, and 24 h following the modeling procedure, respectively. A color-coded iodine map was used to evaluate the myocardial perfusion defects on the 17-segment model. In consensus, two radiologists interpreted all iodine map imaging results from MPI and CCTA. Considering CAG and pathological staining as gold standards, the sensibility and specificity of the CCTA and iodine maps from MPI were evaluated using dual-energy CT. Results Models of acute myocardial infarction were successfully made in five minipigs. Following coronary embolization, dual-energy CT iodine maps showed 45 infarcted segments and 40 non-infarcted segments. Per-segment analysis indicated the sensitivity, specificity, positive predictive value and negative predictive value as 93%, 95%, 95% and 93%, respectively. The corresponding values obtained by per-territory analysis were 100%, 86%, 89% and 100%, with CAG and histopathological findings as reference standards. The effective radiation dose of each dual-energy scan was 3.07±0.85 mSv(2.21-4.49 mSv). Conclusions Dual-energy"one-step"combined CCTA and MPI iodine maps for the detection of acute myocardial infarction via second-generation dual-source CT showed enhanced diagnostic accuracy with CAG and histopathology as gold standards.
Imaging features of digital mammography and sonography on mammary atypical hyperplasia
Cuijun Lin, Lihong Li, Huilian Chen, Zhijun Yi, Baifeng Huang
2015, 39(3): 216-219. doi: 10.3760/cma.j.issn.1673-4114.2015.03.006
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Objective To assess the imaging features of mammary atypical hyperplasia. Methods Sixty-four histologically confirmed mammary atypical hyperplasia cases were imaged using mammography and ultrasonography, and their imaging features were retrospectively studied. Results A total of 8 cases with 84.4% diagnostic rate were mammography positive and ultrasonography negative; 7 cases with 82.8% diagnostic rate were ultrasonography positive and mammography negative; 46 cases with 95.3% diagnostic rate were all mammography and ultrasonography positive; and 3 cases were all mammography and ultrasonography negative but with palpable lesions. Conclusion This study showed that clinical detection and diagnosis of mammary atypical hyperplasia require comprehensive imaging.
Diagnosis of rectal neuroendocrine tumor using CT
Wenfeng Zhu, Haiyang Dai, Xin Li, Hua Zhong, Yujing Zeng, Bowen Lan
2015, 39(3): 220-223. doi: 10.3760/cma.j.issn.1673-4114.2015.03.007
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Objective To investigate CT imaging features of rectal neuroendocrine tumor (RNET) and identify its diagnostic features. Methods CT imaging data of 21 RNET cases confirmed by endoscopy or surgical pathology were retrospectively analyzed. Results Of the 21 cases, 8 were typical carcinoid, 3 were atypical carcinoid, and 10 were poorly differentiated neuroendocrine/small cell carcinoma. The lesions in the lumen were soft nodular-like tissue on plain CT with clear margin and homogeneous density. Enhancement rendered the arterial phase evident and the venous phase moderately visible. A total of 18 cases showed growth in the serous membrane and invasion in the fat around the rectum, 16 cases showed lymph node metastasis around the rectum, and 2 cases exhibited liver metastasis. Conclusions A number of CT imaging features specifically characterized neuroendocrine tumors; however, definitive diagnosis still relies on pathological diagnosis.
Influential factors of solid-phase extraction method to automate the synthesis of 11C-acetate
Lei Zhao, Yan Yang, Hua Sun
2015, 39(3): 224-227,234. doi: 10.3760/cma.j.issn.1673-4114.2015.03.008
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Objective To discuss the factors that affect the synthesis of 11C-acetate via a domestic automated solid-phase extraction method. Methods The synthesis efficiency of 11C-acetate was influenced by the release rate of 11CO2 from the cyclotron target, the release time of 11CO2 by the capture ring, the concentration and volume of tetrahydrofuran(THF) with CH3MgBr, nitrogen current rate and pressure, water in the synthesis system. Thus, these parameters were optimized. Results After performing 18 runs of the conditional parallel experiment, the synthesis efficiency of 11C-acetate was increased to(53.7±3.6)%, and the radiochemical purity was more than 99%. Conclusion The main factors that affect the efficiency of 11C-acetate synthesis were the concentration and volume of CH3MgBr/THF, the current rate of nitrogen, and the pressure of nitrogen.
The preliminary feasibility studies of 4-[18F] fluorobutyric acid and its methyl ester as PET imaging agents
Yonghong Dang, Jiong Cai, Ling Wang, Jingqiao Lyu, Fang Li
2015, 39(3): 228-234. doi: 10.3760/cma.j.issn.1673-4114.2015.03.009
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Objective To synthesize 4-[18F] fluorobutyric acid and its methyl ester automatically using PET-MF-2V-IT-I multifunction synthesizer and to evaluate their feasibility as PET imaging agents. Methods The precursor, methyl 4-bromobutyrate was fluorinated with 18F-. The intermediate, methyl 4-[18F] fluorobutyrate was separated by high pressure liquid chromatography. The components which retention time was from 6.8 to 7.8 min were collected. The components were heated with NaOH solution at 115℃ for 10 min to hydrolyze, and then neutralized with HCl solution. The product, 4-[18F] fluorobutyric acid was obtained. The components were diluted and passed through a C18 cartridge, which was washed with 20 ml water then. The product, methyl 4-[18F] fluorobutyrate was obtained after 0.5 ml ethanol eluted the cartridge and was diluted with saline. The quality controls of both products were done. The clarity was tested visually, the pH value was tested with precise pH paper, and the radiochemical purity and stability were also measured. 4-[18F] fluorobutyric acid(7.4~11.1 MBq) was injected into the C57BL/J mice via tail vein for micro PET imaging at 30 min time-point. Results The whole synthetic procedure periods of 4-[18F] fluorobutyric acid and methyl 4-[18F] fluorobutyrate were 40 min and 20 min separately. The radiochemical yields of the two products were about 35% and 50%(both decay uncorrected) respectively. The pH values were 6.5 and 7.1. The radiochemical purities were both > 95%. Both the product solutions were clear and no particles. Defluorination was observed in these two product solutions 0.5 h later at room temperature. The micro PET imaging showed that the uptake of spine was clearly, which indicated that the imaging agent was defluorinated in vivo, the uptake of intestine was also higher. Conclusion 4-[18F] fluorobutyric acid and its methyl ester could be automatically synthesized on PET-MF-2V-IT-I multifunction synthesizer simply and rapidly. The synthetic yield, radiochemical purity were high. But for their instabilities at room temperature, the two agents were not suitable for further studies as PET imaging agents. But the micro PET imaging suggested the analogs of [18F] fluorobutyric acid may have its potential in diagnosis of intestinal diseases.
Synthesis, hypoxic radiosensitization and biodistribution of N-(5-nitroindazole-3-formyl)tyrosine sodium
Hao Wang, Zewei Zhou, Xiaoliang Zhou
2015, 39(3): 235-238. doi: 10.3760/cma.j.issn.1673-4114.2015.03.010
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Objective To synthesize N-(5-nitroindazole-3-formyl)tyrosine sodium and investigate its hypoxic radiosensitizing effect and biodistribution. Method Synthesized the target compound(N-(5-nitroindazole-3-formyl)tyrosine sodium)using condensing agents, and investigated its radiosensitization under hypoxia using H22 xenograft models and its biodistribution using radioactive iodine labeling. Results The synthesis and structure of the target compound were confirmed. Xenograft models showed that it had a certain radiosensitizing activity and the mean value of sensitization enhancement ratio was 1.5. Biodistribution experiment revealed that it had a good distribution manner, the distribution ratios of tumor to the nervous system and muscle were both greater than 5. Conclusion N-(5-nitroindazole-3-formyl)tyrosine sodium had good radiosensitizing activity and biodistribution manner, and it was worthy of further study.
CT imaging features of duodenal Brunner′s gland adenoma(with 7 cases analysis)
Xin Li, Haiyang Dai, Hua Zhong, Lihong Li
2015, 39(3): 239-241. doi: 10.3760/cma.j.issn.1673-4114.2015.03.011
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Objective To investigate the CT imaging features of duodenal Brunner′s gland adenoma. Methods CT imaging data of 7 pathologically confirmed duodenal Brunner′s gland adenomas were retrospectively analyzed. Results Duodenal Brunner′s gland adenomas were round or strip-like shaped tumors with homogeneous or heterogeneous density, with a clear margin. The size of tumors ranged from 1.5~5.1 cm, and 4.1 cm in average. The solid part of tumors has a similar density compared to the adjacent intestinal wall on plain CT, and has a moderately heterogeneous enhancement in the arterial phase after contrast agent administration. In the portal venous phase, the tumors were progressively but still heterogeneous enhanced. Conclusions There are some specific imaging features of duodenal Brunner′s adenoma. The cognition of its imaging features makes accurate diagnosis possible, but the definitive diagnosis still requires pathological diagnosis.
The application value of 18F-FDG PET/CT in patients with differentiated thyroid cancer of high thyroglobulin level and negative 131I whole body scan
Bin Hu, Jinfeng Wang, Qiufen Mao
2015, 39(3): 242-246, 251. doi: 10.3760/cma.j.issn.1673-4114.2015.03.012
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Objective To estimate the valuate of 18F-FDG PET/CT as a routine examination for the patients with suspected differentiated thyroid carcinoma(DTC) recurrence, accompanied by the increase of thyroglobulin(Tg) and negative 131I whole body scan. Method 32 patients who suffered from DTC receiving post-operative 131I therapy, with increase of Tg and negative 131I whole body scan, were performed 18F-FDG PET/CT, and follow-up continued. Patients were divided into two groups according to the level of Tg:H group(Tg > 10 ng/ml)and L group(Tg < 10 ng/ml). Histopathological examination, ultrasound examination and clinical follow-up were used to verify the result, and assess the clinical value of PET/CT. Result PET/CT imaging results indicated that among 32 patients, there were 20 positive(18 true-positive and 2 false-positive) and 12 negative(4 true-negative and 8 false-negative). Among 18 patients with true positive, 15 cases with local disease, 6 cases with distant metastasis, and 3 patients with both local invasion and distant metastasis. The overall sensitivity, specificity and accuracy were 69.2%, 66.7% and 68.8%, respectively. Compared with the L group, H group developed higher sensitivity(80% versus 33.3%), specificity(100% versus 60%) and accuracy(80.9% versus 45.5%). In 32 patients, 18 cases(56.2%) changed the strategies of clinical treatment, and 12 cases(37.5%) were received the radical operation under guidance. Conclusion 18F-FDG PET/CT can detect and locate accurately for the regional metastasis and recurrence of patients with DTC, accompanied by the increase of serum Tg and negative 131I whole body scan. Therefore, it can be recommended as a routine diagnostic tool.
Review
Development in translational medicine-related mechanisms of radiotherapy for head and neck cancer
Lili Jia, Cuida Meng, Xiaodong Liu, Shumei Ma
2015, 39(3): 247-251. doi: 10.3760/cma.j.issn.1673-4114.2015.03.013
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Head and neck cancer is currently one of the most common tumors worldwide. More than 90% of head and neck tumors are squamous cell carcinoma. Radiotherapy is particularly important in the treatment of head and neck cancer. Current domestic treatment is sole radiotherapy for early tumors, but comprehensive treatment is administered for late tumors. Translational medicine, which closely connects results from studies and clinical medicine, has emerged as a new research focus in recent years. This method is expected to provide basis for target and individual radiotherapy through the detection of target gene mutations, gene single nucleotide polymorphism classification, and mRNA gene expression in tumor tissues of patients. Thus, this method can be used to evidently improve the efficiency of clinical treatment of tumors.
Development of 18F-FDG PET myocardial metabolic imaging in the diagnosis of myocardial survival
Jiao Wang, Jianming Li
2015, 39(3): 252-255,272. doi: 10.3760/cma.j.issn.1673-4114.2015.03.014
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Severe coronary artery disease is the cause of left ventricular dysfunction, and the treatment for this disease is not effective. Many coronary angiographies showed that severe coronary stenosis did not significantly improve heart function after treatment, except for a few patients. Therefore, effective assessment of the myocardial viability status for the coronary revascularization choice and efficacy has significant predictive value. Nuclide myocardial imaging as a noninvasive examination plays an important role in the diagnosis of coronary heart disease, risk stratification, ischemia assessment, prognosis, and so on. 18F-FDG PET imaging of myocardial metabolism can accurately assess the status and proportion of myocardial viability and possesses an important role in the outcome of coronary heart disease and the effect of treatment.
Integrins αvβ3 in molecular imaging and targeted therapy of neoplasms
Jianmin Huang, Peng Xie, Xiaomei Liu, Liping Pan, Jianqing Gao
2015, 39(3): 256-259. doi: 10.3760/cma.j.issn.1673-4114.2015.03.015
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Integrin αvβ3 are heterodimeric transmembrane glycoproteins, consisting of two noncovalently bound transmembrane subunits. It had a high expression on the tumor but it does not expression on the surface of normal blood vessels or the normal organizations or only had a low level expression. It can regulate tumor angiogenesis by cell adhesion. The integrin αvβ3 can specifically recognize and combine with the peptides which containing tripeptide Arg-Gly-Asp(RGD). These RGD peptides are labeled with appropriate nuclide. The PET/CT, SPECT/CT and PET/MRI multimode imaging can be used to examine the tumor integrin αvβ3 expression level. Thus it can be used as a new target for the tumor angiogenesis imaging and therapy. There is a summary on the design of the integrin αvβ3 agents, the choice of appropriate radionuclides and the research direction of these agents.
Late effects of radiotherapy on normal tissue
Wanting Cao, Huanyang Li, Xueying Chen, Silian Fang
2015, 39(3): 260-263. doi: 10.3760/cma.j.issn.1673-4114.2015.03.016
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Normal tissues inevitably exposed to radiation during radiotherapy which may result in tissue injury, and patients′ quality of life would be affected. However, the injury time and degree of tissues were not the same, and the long-term adverse reactions of radiotherapy have remarkable effect on the long-term survivors. This review summarizes the delayed radiation injury effects on different organs.
Mechanism and performance of position radionulide imaging in lung granuloma
Zhenguang Wang, Yu Han
2015, 39(3): 264-267. doi: 10.3760/cma.j.issn.1673-4114.2015.03.017
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18F-FDG PET/CT has been widely used to diagnose benign and malignant lung tumors. 18F-FDG is not a targeted tumor malignancy indicator because highly metabolic inflammatory cells, such as macrophages, lymphocytes, and eosinophils, also exhibit high 18F-FDG uptake. Granulomatous lung inflammation is pathologically characterized by a large amount of metabolic inflammatory cell infiltration and is therefore the leading cause of false positive 18F-FDG PET/CT uptake. This review aims to improve the accuracy of 18F-FDG PET/CT technique in lung tumor diagnosis and help readers understand PET/CT technique and the mechanism of granulomatous lung inflammation.
Development in the study of radium-223 chloride for treating castration-resistant prostate carcinoma with bone metastases
Jicong Gui, Xingdang Liu
2015, 39(3): 268-272. doi: 10.3760/cma.j.issn.1673-4114.2015.03.018
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Prostate carcinoma rates and mortalities are increasing worldwide. The therapeutic landscape of castration-resistant prostate carcinoma(CRPC) has changed rapidly. Radium-223 chloride, which is a radiopharmaceutical agent, targets bone metastasis by emitting high-energy alpha-particles with extremely short range(< 100 μm). This chemical is effective in reducing mortality without increasing toxicity. Thus, this agent has the potential to become a new alternative for treating patients with CRPC. The Food and Drug Administration approved radium-223 dichloride for treating patients with CRPC, symptomatic bone metastases, and unknown visceral metastatic disease in 2013. Therefore, combination and sequencing strategies will be future research directions.
2015, 39(3): 273-276. doi: 10.3760/cma.j.issn.1673-4114.2015.03.019
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