乳腺癌淋巴微转移模型的建立及皮内与静脉注射~(18)F-脱氧葡萄糖的诊断效果
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摘要
目的:探讨乳腺癌小鼠区域性局部皮内和静脉注射~(18)F-脱氧葡萄糖(~(18)F-fluorodeoxyglucose,~(18)F-FDG)后瘤周淋巴结PET/CT成像的差异,评估~(18)F-FDG在肿瘤淋巴结微转移中的成像效果。方法:构建4T1原位乳腺癌淋巴结微转移模型,区域性局部皮内和次日静脉注射~(18)F-FDG,进行小动物PET/CT显像,对淋巴结摄取~(18)F-FDG较高者隔日再行瘤周局部皮内注射锝硫胶体(technetium sulfur colloid,99mTc-SC)后行小动物SPECT/CT成像。显像完成后,取淋巴结组织进行H-E染色,以及上皮细胞角蛋白5/6(cytokeratin 5/6,CK5/6)和葡萄糖转运蛋白1(glucose transporter-1,Glut-1)免疫组织化学染色。结果:局部皮内注射时,有微转移的小鼠瘤周淋巴结摄取~(18)F-FDG异常增高,ID%/g值为19.2±2.0(n=2),显著高于对照(自身对照时对侧淋巴结;ID%/g值为6.8±0.4)和无转移小鼠(ID%/g值为7.2±0.4)相同位置淋巴结(P<0.001)。静脉注射时,未发现任何小鼠淋巴结摄取异常增高(ID%/g值为2.5±0.5;P=0.870)。局部皮内注射99mTc-SC时,可观测到多个腋淋巴结,其中1个瘤周淋巴结与~(18)F-FDG高摄取淋巴结位置相吻合。H-E染色和CK5/6免疫组织化学染色证实,~(18)F-FDG高摄取的淋巴结为发生微转移的淋巴结。结论:区域性局部皮内注射~(18)F-FDG能定性前哨淋巴结,比静脉注射法早期发现肿瘤微转移淋巴结。
Objective: To investigate the difference in the identification of lymph node micrometastasis between regional subcutaneous injection and intravascular injection of ~(18)F-fluorodeoxyglucose(~(18)F-FDG) by PET/CT imaging in mouse breast cancer. Methods: The mouse 4 T1 breast cancer lymph node micrometastasis model was established. The regional subcutaneous and intravascular injection of ~(18)F-FDG was performed for PET/CT imagingin two day, respectively. For the higher ~(18)F-FDG uptake in lymph node of mice, SPECT/CT imaging was also performed by subcutaneous injection of technetium sulfur colloi(99 mTc-SC). H-E staining and immunohistochemistry of epithelial cytokeratin 5/6(CK5/6) and glucose transporter 1(Glut-1) were measured. Results: The uptake value(ID%/g) of ~(18)F-FDG in lymph nodes was 19.2±2.0(n=2) by subcutaneous injection in micrometastasis group, which was significantly higher than the contralateral ones(ID%/g of 6.8±0.4) and those without micrometastasis(ID%/g of 7.2±0.4)(P<0.000 1). No increased uptake of ~(18)F-FDG was observed in any mouse lymph node(ID%/g of 2.5±0.5)(P=0.870) by intravascular injection. Moreover, SPECT/CT imaging with 99 mTc-SC revealed multiple axillary lymph nodes, one of which had a well-matched lymph node with high ~(18)F-FDG uptake. H-E staining and immunohistochemistry of CK5/6 confirmed that high ~(18)F-FDG uptake in lymph nodes revealed micrometastatic. Conclusion: Regional subcutaneous injection of ~(18)F-FDG can qualitatively identify micrometastatic sentinel lymph nodes earlier than intravenous injection, which is worthy of clinical application.
Objective: To investigate the difference in the identification of lymph node micrometastasis between regional subcutaneous injection and intravascular injection of ~(18)F-fluorodeoxyglucose(~(18)F-FDG) by PET/CT imaging in mouse breast cancer. Methods: The mouse 4 T1 breast cancer lymph node micrometastasis model was established. The regional subcutaneous and intravascular injection of ~(18)F-FDG was performed for PET/CT imagingin two day, respectively. For the higher ~(18)F-FDG uptake in lymph node of mice, SPECT/CT imaging was also performed by subcutaneous injection of technetium sulfur colloi(99 mTc-SC). H-E staining and immunohistochemistry of epithelial cytokeratin 5/6(CK5/6) and glucose transporter 1(Glut-1) were measured. Results: The uptake value(ID%/g) of ~(18)F-FDG in lymph nodes was 19.2±2.0(n=2) by subcutaneous injection in micrometastasis group, which was significantly higher than the contralateral ones(ID%/g of 6.8±0.4) and those without micrometastasis(ID%/g of 7.2±0.4)(P<0.000 1). No increased uptake of ~(18)F-FDG was observed in any mouse lymph node(ID%/g of 2.5±0.5)(P=0.870) by intravascular injection. Moreover, SPECT/CT imaging with 99 mTc-SC revealed multiple axillary lymph nodes, one of which had a well-matched lymph node with high ~(18)F-FDG uptake. H-E staining and immunohistochemistry of CK5/6 confirmed that high ~(18)F-FDG uptake in lymph nodes revealed micrometastatic. Conclusion: Regional subcutaneous injection of ~(18)F-FDG can qualitatively identify micrometastatic sentinel lymph nodes earlier than intravenous injection, which is worthy of clinical application.
引文
[1]SINGNURKAR A,POON R,METSER U.Comparison of 18F-FDG-PET/CT and 18F-FDG-PET/MR imaging in oncology:a systematic review[J].Ann Nucl Med,2017,31(5):366-378.
[2]GROHEUX D,MANKOFF D,ESPIéM,et al.18F-FDG PET/CT in the early prediction of pathological response in aggressive subtypes of breast cancer:review of the literature and recommendations for use in clinical trials[J].Eur J Nucl Med Mol I,2016,43(5):983-993.
[3]KITAJIMA K,FUKUSHIMA K,MIYOSHI Y,et al.Diagnostic and prognostic value of 18F-FDG PET/CT for axillary lymph node staging in patients with breast cancer[J].Jpn J Radiol,2016,34(3):220-228.
[4]COOPER K I,HARMAN S,MENG Y,et al.Positron emission tomography(PET)for assessment of axillary lymph node status in early breast cancer:a systematic review and meta-analysis[J].Eur J Surg Oncol,2011,37(3):187-198.
[5]ORSARIA P,CHIARAVALLOTI A,FIORENTINI A,et al.PET probe-guided surgery in patients with breast cancer:proposal for a methodological approach[J].In Vivo,2017,31(1):101-110.
[6]THOREK D L,ABOU D S,BCATTIC B J,et al.Positron lymphography:multimodal,high-resolution,dynamic mapping and resection of lymph nodes after intradermal injection of 18F-FDG[J].J Nucl Med,2012,53(9):1438-1445.
[7]BAO L,HAQUE A,JACKSON K,et al.Increased expression of P-glycoprotein is associated with doxorubicin chemoresistance in the metastatic 4T1 breast cancer model[J].Am J Pathol,2011,178(2):838-851.
[8]GRADISHAR W J,ANDERSON B O,BALASSANIAN R,et al.Invasive breast cancer version 1.2016,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2016,14(3):324-354.
[9]章英剑,潘张弛,周敏,等.乳腺癌前哨淋巴结显像研究[J].中华核医学杂志,2003,23(4):197-200.
[10]刘哲斌,吴炅,黄晓燕,等.乳腺癌前哨淋巴结活检中亚甲蓝与亚甲蓝、同位素联合示踪的比较研究[J].中华普通外科杂志,2007,22(11):840-843.
[11]孙晓,王永胜,宋现让,等.乳腺癌前哨淋巴结术中分子诊断的价值[J].中华肿瘤杂志,2011,33(2):138-141.
[12]AHMED M,PURUSHOTHAM A D,DOUEK M.Novel techniques for sentinel lymph node biopsy in breast cancer:a systematic review[J].Lancet Oncol,2014,15(8):351-362.
[13]陆晓聆,袁慧瑜,曹天野,等.99mTc-硫胶体不同注射体积在乳腺癌前哨淋巴结定位中的对比分析[J].肿瘤影像学杂志,2017,26(3):193-198.
[2]GROHEUX D,MANKOFF D,ESPIéM,et al.18F-FDG PET/CT in the early prediction of pathological response in aggressive subtypes of breast cancer:review of the literature and recommendations for use in clinical trials[J].Eur J Nucl Med Mol I,2016,43(5):983-993.
[3]KITAJIMA K,FUKUSHIMA K,MIYOSHI Y,et al.Diagnostic and prognostic value of 18F-FDG PET/CT for axillary lymph node staging in patients with breast cancer[J].Jpn J Radiol,2016,34(3):220-228.
[4]COOPER K I,HARMAN S,MENG Y,et al.Positron emission tomography(PET)for assessment of axillary lymph node status in early breast cancer:a systematic review and meta-analysis[J].Eur J Surg Oncol,2011,37(3):187-198.
[5]ORSARIA P,CHIARAVALLOTI A,FIORENTINI A,et al.PET probe-guided surgery in patients with breast cancer:proposal for a methodological approach[J].In Vivo,2017,31(1):101-110.
[6]THOREK D L,ABOU D S,BCATTIC B J,et al.Positron lymphography:multimodal,high-resolution,dynamic mapping and resection of lymph nodes after intradermal injection of 18F-FDG[J].J Nucl Med,2012,53(9):1438-1445.
[7]BAO L,HAQUE A,JACKSON K,et al.Increased expression of P-glycoprotein is associated with doxorubicin chemoresistance in the metastatic 4T1 breast cancer model[J].Am J Pathol,2011,178(2):838-851.
[8]GRADISHAR W J,ANDERSON B O,BALASSANIAN R,et al.Invasive breast cancer version 1.2016,NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2016,14(3):324-354.
[9]章英剑,潘张弛,周敏,等.乳腺癌前哨淋巴结显像研究[J].中华核医学杂志,2003,23(4):197-200.
[10]刘哲斌,吴炅,黄晓燕,等.乳腺癌前哨淋巴结活检中亚甲蓝与亚甲蓝、同位素联合示踪的比较研究[J].中华普通外科杂志,2007,22(11):840-843.
[11]孙晓,王永胜,宋现让,等.乳腺癌前哨淋巴结术中分子诊断的价值[J].中华肿瘤杂志,2011,33(2):138-141.
[12]AHMED M,PURUSHOTHAM A D,DOUEK M.Novel techniques for sentinel lymph node biopsy in breast cancer:a systematic review[J].Lancet Oncol,2014,15(8):351-362.
[13]陆晓聆,袁慧瑜,曹天野,等.99mTc-硫胶体不同注射体积在乳腺癌前哨淋巴结定位中的对比分析[J].肿瘤影像学杂志,2017,26(3):193-198.