~(18)F-NaF注射液的制备及新西兰兔骨折显像
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摘要
由外伤或肿瘤骨转移造成的隐匿性骨折和愈合情况的准确诊断对制定合适的治疗方案具有非常重要的意义。为考查~(18)F-NaF PET显像用于骨折诊断的诊断效能,本研究制备了~(18)F-NaF注射液,并对其进行了质量控制和稳定性研究,然后建立新西兰兔骨折动物模型,模型建立约2周后进行了~(18)F-NaF PET显像和~(99)Tc~m-亚甲基二磷酸盐(~(99)Tc~m-MDP)SPECT显像的自身对照实验,并对显像效果进行了比较。结果表明:~(18)F-NaF的产量大于37 GBq,各项检验结果均符合质控要求,40℃下放置8 h和30℃下放置10 h所有检验结果均无明显变化;~(18)F-NaF PET和~(99)Tc~m-MDP SPECT两种显像方式均可见全身骨骼,骨折部位呈明显放射性浓聚,但~(18)F-NaF给药后30 min即可进行PET显像,骨折部位显示更为清晰,骨折部位与对侧正常骨骼的放射性摄取比(T/NT)明显高于~(99)Tc~m-MDP,而~(99)Tc~m-MDP需在给药后2 h才能进行SPECT显像。本研究表明~(18)F-NaF PET对骨折的显像性能优于~(99)Tc~m-MDP,可明显提高检查流通量和诊断效能。
The accurate diagnosis of the minute fractures and healing caused by trauma or tumor bone metastasis is very important for the development of appropriate treatment. In order to investigate the efficiency of ~(18)F-NaF PET imaging for fracture diagnosis, ~(18)F-NaF injection was prepared, and the quality control and stability were studied. Self-controlled study between ~(18)F-NaF PET imaging and ~(99)Tc~m-MDP SPECT imaging after two weeks of the establishment of New Zealand rabbit fracture model was carried out. The results show that the production of ~(18)F-NaF is more than 37 GBq, all of the test results conform to the requirements of the quality control, and the test results are no significant changes under the conditions of 40 ℃ for 8 h and 30 ℃ for 10 h. The results of imaging show that the whole body skeleton is visible in both of ~(99)Tc~m-MDP SPECT and ~(18)F-NaF PET imaging, and high radioactive uptakes can be detected in fracture position. But PET imaging can be performed after ~(18)F-NaF injection for 30 min, and fracture is more clearly displayed than SPECT imaging, while SPECT imaging can be performed after ~(99)Tc~m-MDP injection for 2 h. The radioactive uptake ratio(T/NT) between the fractured and the contralateral normal bones of ~(18)F-NaF PET imaging is significantly higher than that of ~(99)Tc~m-MDP imaging. This study indicates that ~(18)F-NaF PET is superior to ~(99)Tc~m-MDP SPECT for fracture imaging.
The accurate diagnosis of the minute fractures and healing caused by trauma or tumor bone metastasis is very important for the development of appropriate treatment. In order to investigate the efficiency of ~(18)F-NaF PET imaging for fracture diagnosis, ~(18)F-NaF injection was prepared, and the quality control and stability were studied. Self-controlled study between ~(18)F-NaF PET imaging and ~(99)Tc~m-MDP SPECT imaging after two weeks of the establishment of New Zealand rabbit fracture model was carried out. The results show that the production of ~(18)F-NaF is more than 37 GBq, all of the test results conform to the requirements of the quality control, and the test results are no significant changes under the conditions of 40 ℃ for 8 h and 30 ℃ for 10 h. The results of imaging show that the whole body skeleton is visible in both of ~(99)Tc~m-MDP SPECT and ~(18)F-NaF PET imaging, and high radioactive uptakes can be detected in fracture position. But PET imaging can be performed after ~(18)F-NaF injection for 30 min, and fracture is more clearly displayed than SPECT imaging, while SPECT imaging can be performed after ~(99)Tc~m-MDP injection for 2 h. The radioactive uptake ratio(T/NT) between the fractured and the contralateral normal bones of ~(18)F-NaF PET imaging is significantly higher than that of ~(99)Tc~m-MDP imaging. This study indicates that ~(18)F-NaF PET is superior to ~(99)Tc~m-MDP SPECT for fracture imaging.
引文
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[9] 张宏波,韦福康,袁朝新,等.骨折超声显像的实验研究[J].中国超声医学杂志,2002,18(9):649-652.ZHANG Hongbo,WEI Fukang,YUAN Chao-xin,et al.Experimental study on ultrasonograhy of fractures[J].Chinese Journal of Ultrasound in Medicine,2002,18(9):649-652(in Chinese).
[10] 王荣福,安锐.核医学[M].9版.北京:人民卫生出版社,2018:137-157.
[11] SHIRRMERSTER H,GUHLMANN A,SLSNER K,et al.Sensitivity in detecting osseous lesions depends on anatomic localization:Planar bone scintigraphy versus 18F PET[J].Journal of Nuclear Medicine,1999,40(10):1 623-1 629.
[12] JADVAR H,DESAI B,JI L,et al.Prospective evaluation of 18F-NaF and 18F-FDG PET/CT in detection of occult metastatic disease in biochemical recurrence of prostate cancer[J].Clinical Nuclear Medicine,2012,37(7):637-643.
[13] LANGSTEGER W,REZAEE A,PIRICH C,et al.18F-NaF-PET/CT and 99Tcm-MDP bone scintigraphy in the detection of bone metastases in prostate cancer[J].Seminars in Nuclear Medicine,2016,46(6):491-501.
[14] MARINA B S,MARCELLA A S,EDUARDO S V,et al.Synthesis,quality control and dosimetry of the radiopharmaceutical 18F-sodium fluoride produced at the center for development of nuclear technology-CDTN[J].Brazilian Journal of Pharmaceutical Sciences,2010,46(3):563-569.
[15] HOCKLEY B G,JHSCOTT P.An automated method for preparation of [18F] sodium fluoride for injection,USP to address the technetium-99m isotope shortage[J].Applied Radiation and Isotopes,2010,68(1):117-119.
[16] 郭飞虎,李明光,李光,等.PET显像剂18F-氟化钠的制备、作用机制和临床应用[J].核化学与放射化学,2017,39(2):138-144.GUO Feihu,LI Mingguang,LI Guang,et al.The preparation,imaging mechanism and clinical application of PET imaging agent sodium [18F] fluoride[J].Journal of Nuclear and Radiochemistry,2017,39(2):138-144(in Chinese).
[17] BLAKE G M,PARK-HOLOHAN S J,COOK G J,et al.Quantitative studies of bone with the use of 18F-fluoride and 99Tcm-methylene diphos-phonate[J].Seminars in Nuclear Medicine,2001,31(1):28-49.
[2] BLAU M,GANATRA R,BENDER M A.18F-fluoride for bone imaging[J].Seminars in Nuclear Medicine,1972,2(1):31-37.
[3] SUBRAMANIAN G,MCAFEE J G.A new complex of 99Tcm for skeletal imaging[J].Radiology,1971,99(1):192-196.
[4] SATYAMURTHY N,PHELPS M E,BARRIO J R.Electronic fenerators for the production of positron-emitter labeled radiopharmaceuticals:Where would PET be without them?[J].Clinical Positron Imaging,1999,2(5):233-253.
[5] 张胤,陈跃.18F-氟化钠PET/CT诊断肿瘤骨转移应用进展[J].国际放射医学核医学杂志,2015,39(1):96-102.ZHANG Yin,CHEN Yue.Application progress of 18F-NaF PET/CT in the diagnosis of neoplasm metastases[J].International Journal of Radiation Medicine and Nuclear Medicine,2015,39(1):96-102(in Chinese).
[6] WOOTTON R,DORE C.The single-passage extraction of 18F in rabbit bone[J].Clinical Physics and Physiological Measurement,1986,7(4):333-343.
[7] 叶谦,董海锋,王卫伟,等.放射性核素骨显像在骨折诊断中的应用[J].创伤外科杂志,2007,9(6):530-533.YE Qian,DONG Haifeng,WANG Weiwei,et a1.Application of radionuclide bone imaging in the diagnosis of fracture[J].Journal of Traumatic Surgery,2007,9(6):530-533(in Chinese).
[8] 刘志.应力性骨折早期影像学分析[J].中华临床医师杂志:电子版,2014,8(18):75-78.LIU Zhi.Early imaging analysis of stress bone injury[J].Chinese Journal of Clinicians:Electronic Edition,2014,8(18):75-78(in Chinese).
[9] 张宏波,韦福康,袁朝新,等.骨折超声显像的实验研究[J].中国超声医学杂志,2002,18(9):649-652.ZHANG Hongbo,WEI Fukang,YUAN Chao-xin,et al.Experimental study on ultrasonograhy of fractures[J].Chinese Journal of Ultrasound in Medicine,2002,18(9):649-652(in Chinese).
[10] 王荣福,安锐.核医学[M].9版.北京:人民卫生出版社,2018:137-157.
[11] SHIRRMERSTER H,GUHLMANN A,SLSNER K,et al.Sensitivity in detecting osseous lesions depends on anatomic localization:Planar bone scintigraphy versus 18F PET[J].Journal of Nuclear Medicine,1999,40(10):1 623-1 629.
[12] JADVAR H,DESAI B,JI L,et al.Prospective evaluation of 18F-NaF and 18F-FDG PET/CT in detection of occult metastatic disease in biochemical recurrence of prostate cancer[J].Clinical Nuclear Medicine,2012,37(7):637-643.
[13] LANGSTEGER W,REZAEE A,PIRICH C,et al.18F-NaF-PET/CT and 99Tcm-MDP bone scintigraphy in the detection of bone metastases in prostate cancer[J].Seminars in Nuclear Medicine,2016,46(6):491-501.
[14] MARINA B S,MARCELLA A S,EDUARDO S V,et al.Synthesis,quality control and dosimetry of the radiopharmaceutical 18F-sodium fluoride produced at the center for development of nuclear technology-CDTN[J].Brazilian Journal of Pharmaceutical Sciences,2010,46(3):563-569.
[15] HOCKLEY B G,JHSCOTT P.An automated method for preparation of [18F] sodium fluoride for injection,USP to address the technetium-99m isotope shortage[J].Applied Radiation and Isotopes,2010,68(1):117-119.
[16] 郭飞虎,李明光,李光,等.PET显像剂18F-氟化钠的制备、作用机制和临床应用[J].核化学与放射化学,2017,39(2):138-144.GUO Feihu,LI Mingguang,LI Guang,et al.The preparation,imaging mechanism and clinical application of PET imaging agent sodium [18F] fluoride[J].Journal of Nuclear and Radiochemistry,2017,39(2):138-144(in Chinese).
[17] BLAKE G M,PARK-HOLOHAN S J,COOK G J,et al.Quantitative studies of bone with the use of 18F-fluoride and 99Tcm-methylene diphos-phonate[J].Seminars in Nuclear Medicine,2001,31(1):28-49.