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乳腺癌是女性常见的恶性肿瘤之一,发病率为29%[1]。全球每年新增乳腺癌病例115万,占全部女性肿瘤患者例数的23%[2]。20~59岁女性因癌症死亡的原因中乳腺癌占首位[3]。因此乳腺癌早期精准诊疗能够提高患者生活质量和减少病死率。乳腺超声检查是筛查乳腺癌的常规方法,通过声像图病灶的特征进行乳腺影像报告和数据系统(breast imaging reporting and data system,BI-RADS)分级。其中,BI-RADS 4级提示可疑恶性,恶性可能性为3%~94%,跨度较大,并且超声征象良恶性病变表现不典型时,BI-RADS分级易受操作者临床经验的影响。分子影像是将分子生物学和影像技术相结合,在分子和细胞水平观察生物体的生物学行为,为临床提供更多的解剖和功能信息[4-5]。整合素αvβ3是一种跨膜异二聚体受体,在正常细胞表面低表达,而高表达于肿瘤细胞表面及新生血管内皮细胞[6-7]。小分子肽Arg-Gly-Asp(RGD)与整合素αvβ3具有高度亲和力及结合特异性[8],可以实现无创血管生成显像。99Tcm-联肼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体(99Tcm-3PRGD2)是一种RGD环肽二聚体,标记简单,高效且可重复性强,近年来已被应用到临床,尤其在肺癌、乳腺癌诊断方面发挥着一定的作用[9-10]。此外,大量研究结果表明肿瘤新生血管与转移和预后关系密切[11-14]。我们旨在探讨99Tcm-3PRGD2整合素受体显像在鉴别乳腺良恶性病变中的价值及与超声检查的对比研究。
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45例入选病例,经病理检查共发现56个病灶,其中,35个病灶为乳腺癌,21个病灶为良性病变。有2例双侧乳腺癌、5例乳腺癌伴对侧良性结节、2例双灶乳腺癌伴对侧良性结节。超声BI-RADS 4级病灶中有7例声像图表现为边界尚清,部分有浅分叶,经病理证实为纤维腺瘤,99Tcm-3PRGD2 SPECT/CT表现为略有显像剂摄取,T/NT值为1.4~2.5;超声BI-RADS 3级病灶中有5例声像图表现为病灶>3 cm,病灶回声与周围腺体组织回声相似,对比不明显,易误诊为纤维腺瘤,经病理证实为浸润性导管癌,99Tcm-3PRGD2 SPECT/CT表现为类圆形显像剂明显摄取,T/NT值为3.5~4.9;有2例乳腺腺病、2例脂肪坏死伴炎症反应病灶,2例乳腺增生伴腺瘤形成超声声像图提示BI-RADS 3级,99Tcm-3PRGD2 SPECT/CT显像可见病灶显像剂摄取,T/NT值为3.1~3.3。此外,有6例病灶在全身显像位于肝脏,经俯卧位SPECT/CT显像定位于右乳。99Tcm-3PRGD2 SPECT/CT阳性判断标准为2 h显像半定量指标T/NT值≥2.9;超声检查阳性判断标准为BI-RADS 4级及以上。病理类型与超声检查、99Tcm-3PRGD2 SPECT/CT的诊断结果见表 1。
病理类型 病理检查 99Tcm-3PRGD2
SPECT/CT超声检查 阳性 阴性 阳性 阴性 浸润性导管癌 35 29 6 30 5 纤维腺瘤 14 0 14 7 7 乳腺腺病 2 2 0 0 2 乳腺增生伴腺瘤形成 3 2 1 0 3 脂肪坏死伴炎症反应 2 2 0 0 2 总计 56 35 21 37 19 注:表中,99Tcm-3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影术 表 1 56个乳腺占位病变病理类型与不同检查方法的诊断结果(个)
Table 1. Pathology classification of 56 breast lesions and the results of different inspection method(cases)
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99Tcm-3PRGD2 2 h SPECT/CT经病理证实的乳腺恶性病灶T/NT值(3.92±1.67)高于良性病灶T/NT值(2.04±0.46),且差异有统计学意义(Z=-3.77,P=0.00)。良性病变的典型病例见图 1,乳腺癌典型病例见图 2。取约登指数最大时的临界值2.9,99Tcm-3PRGD2 SPECT/CT显像诊断的灵敏度、特异度、准确率分别为82.9%(29/35)、71.4%(15/21)、78.6%(44/56),诊断乳腺良恶性病变受试者工作特征曲线(receiver operating characteristic curve,ROC曲线)下面积为0.77。超声诊断乳腺良恶性病变ROC曲线下面积为0.76,其诊断的灵敏度、特异度、准确率分别为85.7%(30/35)、66.7%(14/21)、78.6%(44/56)。99Tcm-3PRGD2 SPECT/CT显像与超声诊断效能相近,差异无统计学意义(χ2=0.05,P>0.05)。超声+99Tcm-3PRGD2 SPECT/CT联合检查可提高乳腺良恶性诊断的准确率(92.9%,52/56),且分别与超声检查、99Tcm-3PRGD2 SPECT/CT显像比较,差异均有统计学意义(χ2=77.17、74.87,均P < 0.05)(表 2)。
图 1 46岁女性患者乳腺99Tcm-3PRGD2整合素受体SPECT/CT显像图、超声BI-RADS 4a级声像图和病理图 图中,A:肘静脉注射99Tcm-3PRGD2 2 h行全身显像,全身未见明显显像剂分布异常影;B:胸部局部SPECT显像,乳腺区域未见明显显像剂分布异常影;C:CT定位像可见左侧乳腺类圆形软组织密度影;D:SPECT/CT融合显像,T/NT值为1.1;E:早期15 min SPECT静态显像,胸部未见明显显像剂分布增高影;F:乳腺超声示左乳外上象限无回声区,边界尚规则,BI-RADS 4a级;G:病理结果为左乳纤维腺瘤(苏木精-伊红染色,伊100);99Tcm-3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影;BI-RADS:乳腺影像报告和数据系统。
Figure 1. years old females with the breast integrin receptor imaging, of 99Tcm-3PRGD2, ultrasonography of BI-RADS4a and pathology
图 2 64岁女性患者乳腺99Tcm-3PRGD2整合素受体SPECT/CT显像图、超声BI-RADS 4c级声像图和病理图 图中,A:肘静脉注射99Tcm-3PRGD2 2 h行全身显像,于胸部右侧可见点状显像剂分布增高影;B:胸部局部SPECT显像,右侧乳腺区域可见显像剂分布增高影;C:CT定位像可见右侧乳腺类圆形软组织密度影;D:SPECT/CT融合显像,T/NT值为5.96;E:早期5 min SPECT静态显像,胸部右侧可见片状显像剂分布增高影;F:乳腺超声示右乳外上象限无回声区,呈毛刺征,BI-RADS 4c级;G:病理结果为右乳浸润性导管癌(苏木精-伊红染色,伊100);99Tcm-3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影术;BI-RADS:乳腺影像报告和数据系统。
Figure 2. 64 years old females with the breast integrin receptor imaging of 99Tcm-3PRGD2, ultrasonography of BI-RADS 4c and pathology
显像方法 灵敏度/% 特异度/% 准确率/% ROC曲线下面积 标准误 95%置信区间 下限 上限 超声检查 85.7 66.7 78.6a 0.76 0.07 0.62 0.90 99Tcm-3PRGD2 SPECT/CT 82.9 71.4 78.6a 0.77 0.07 0.63 0.91 超声检查+99Tcm-3PRGD2 SPECT/CT 94.3 90.5 92.9 0.92 0.04 0.84 1.00 注:表中,a:与超声检查+99Tcm-3PRGD2 SPECT联合显像比较,准确率的差异有统计学意义(χ2=77.17、74.87,均P < 0.05)。99Tcm- 3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影术;ROC曲线:受试者工作特征曲线 表 2 99Tcm-3PRGD2 SPECT/CT显像与超声检查诊断效能的比较
Table 2. Comparation of the diagnostic efficiency of 99Tcm-3PRGD2 SPECT/CT imaging and ultrasonography
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99Tcm-3PRGD2 SPECT早期15 min静态显像阳性组和阴性组中的病灶在2 h显像的T/NT值分别为4.59±1.49、3.28±1.27,阳性组高于阴性组,差异有统计学意义(Z=-3.90,P=0.01)。经病理证实的35个恶性病灶中有26个病灶早期静态显像阳性,典型病例见图 2;病理结果证实的14个纤维腺瘤早期静态显像为阴性,其中超声检查为BI-RADS 4a级病灶3个、BI-RADS 4b级病灶4个、BI-RADS 3级病灶7个,典型病例见图 1、图 3。
图 3 43岁女性患者乳腺99Tcm-3PRGD2整合素受体SPECT/CT显像图、超声BI-RADS 4b级声像图和病理图 图中,A:肘静脉注射99Tcm-3PRGD2 2 h行全身显像,于胸部左侧可见点状显像剂分布增高影;B:胸部局部SPECT显像,左侧乳腺区域可见显像剂分布增高影;C:CT定位像可见左侧乳腺类圆形软组织密度影;D:SPECT/CT融合显像,T/NT值为3.1;E:早期5 min SPECT静态显像,胸部未见明显显像剂分布增高影;F:乳腺超声示左乳外上象限无回声区,边界欠规整,BI -RADS 4b级;G:病理结果为左乳纤维腺瘤(苏木精-伊红染色,伊100);99Tcm-3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影;BI-RADS:乳腺影像报告和数据系统。
Figure 3. 43 years old females with the breast integrin receptor imaging of 99Tcm-3PRGD2, ultrasonography of BI-RADS 4b and pathology
99Tcm-3PRGD2整合素受体显像鉴别乳腺良恶性病变的价值及与超声检查的对比研究
The evaluation of 99Tcm-3PRGD2 integrin receptor imaging in the differential diagnosis in benign and malignant breast lesions comparision with ultrasound
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摘要:
目的探讨99Tcm-3PRGD2整合素受体显像鉴别乳腺良恶性病变的价值及与超声检查的对比研究。 方法收集2016年10月至2017年6月因乳腺结节或肿块拟行穿刺或手术治疗的女性患者,行乳腺超声检查,选取超声提示病灶直径>1 cm的45例患者经肘静脉注射99Tcm-3PRGD2(740~925 MBq)后行早期15 min SPECT静态显像及2 h SPECT/CT俯卧位显像。以病理结果为“金标准”,采用半定量分析指标T/NT值建立诊断阈值并进行诊断效能分析。组间比较采用独立样本非参数检验Mann-Whitney U方法;诊断效能比较采用χ2检验。 结果45例患者经病理学检查共发现56个病灶,其中,35个病灶为乳腺癌,21个病灶为良性病变。99Tcm-3PRGD2 2 h SPECT/CT显像的乳腺恶性病灶T/NT值(3.92±1.67)高于良性病灶T/NT值(2.04±0.46),且差异有统计学意义(Z=-3.77,P=0.00)。取约登指数最大时的临界值2.9,99Tcm-3PRGD2 SPECT/CT显像的灵敏度、特异度、准确率分别为82.9%、71.4%、78.6%,诊断乳腺良恶性病变受试者工作特征(ROC)曲线下面积为0.77;超声诊断乳腺良恶性病变ROC曲线下面积为0.76,其灵敏度、特异度、准确率分别为85.7%、66.7%、78.6%。99Tcm-3PRGD2 SPECT/CT与超声诊断效能相近(χ2=0.05,P>0.05)。超声+99Tcm-3PRGD2 SPECT/CT联合检查可提高乳腺良恶性诊断的准确率(92.9%),分别与二者比较差异均有统计学意义(χ2=77.17、74.87,均P < 0.05)。 结论99Tcm-3PRGD2整合素受体显像可以从肿瘤血管生成角度鉴别乳腺良恶性病变,提供解剖及功能信息,尤其对于超声声像图表现不典型时,可进一步鉴别良恶性,减少患者不必要的穿刺等有创性检查。 -
关键词:
- 乳腺肿瘤 /
- 单光子发射计算机体层摄影术 /
- 超声检查 /
- 整合素αvβ3受体
Abstract:ObjectiveTo evaluate the diagnostic efficacy of 99Tcm-3PRGD2 integrin receptor imaging in the differential diagnosis of benign and malignant lesions in comparison with ultrasound. MethodsForty-five females(53.0±9.5 years old) with breast nodules or masses measuring over 1 cm from October 2016 to June 2017, which were diagnosed through ultrasound, underwent early imaging via 99Tcm-3PRGD2 (740-925 MBq) for 15 min and then SPECT/CT in prone position after 2 h. The pathology was the gold standard. Then, a semi-quantitative method was used to evaluate the values of 99Tcm-3PRGD2 integrin receptor imaging of breast lesions and compare them with ultrasound results. The Mann-Whitney U test was used to compare the groups. Lastly, diagnostic efficacy was compared using a chi-square test. Results99Tcm-3PRGD2 integrin receptor imaging identified 56 lesions in 45 patients, 35 of which were malignant and 21 were benign. The T/NT values of the malignant lesions were significantly higher than those of the benign lesions(Z=-3.77, P=0.00) in the SPECT/CT images. The sensitivity, specificity, and accuracy of 99Tcm-3PRGD2 and ultrasound were 82.9%, 71.4%, and 78.6%, and 85.7%, 66.7%, and 78.6%, respectively. The critical value was 2.9 with the maximal Youden index. Furthermore, areas under the ROC curve for 99Tcm-3PRGD2 and ultrasound were 0.77 and 0.76, respectively. The diagnostic efficacy of 99Tcm-3PRGD2 was similar to that of ultrasonography(χ2=0.05, P>0.05). Thus, combining the two methods can improve the accuracy of diagnosis(92.9%) compare with ultrasound and 99Tcm-3PRGD2 (χ2=77.14, 74.87, all P < 0.05). Conclusions99Tcm-3PRGD2 integrin receptor imaging can identify benign and malignant breast lesions from an angiogenesis perspective with anatomical and functional information. Moreover, this technique can further identify benign and malignant lesions to reduce unnecessary punctures when ultrasonograms are unavailable. -
图 1 46岁女性患者乳腺99Tcm-3PRGD2整合素受体SPECT/CT显像图、超声BI-RADS 4a级声像图和病理图 图中,A:肘静脉注射99Tcm-3PRGD2 2 h行全身显像,全身未见明显显像剂分布异常影;B:胸部局部SPECT显像,乳腺区域未见明显显像剂分布异常影;C:CT定位像可见左侧乳腺类圆形软组织密度影;D:SPECT/CT融合显像,T/NT值为1.1;E:早期15 min SPECT静态显像,胸部未见明显显像剂分布增高影;F:乳腺超声示左乳外上象限无回声区,边界尚规则,BI-RADS 4a级;G:病理结果为左乳纤维腺瘤(苏木精-伊红染色,伊100);99Tcm-3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影;BI-RADS:乳腺影像报告和数据系统。
Figure 1. years old females with the breast integrin receptor imaging, of 99Tcm-3PRGD2, ultrasonography of BI-RADS4a and pathology
图 2 64岁女性患者乳腺99Tcm-3PRGD2整合素受体SPECT/CT显像图、超声BI-RADS 4c级声像图和病理图 图中,A:肘静脉注射99Tcm-3PRGD2 2 h行全身显像,于胸部右侧可见点状显像剂分布增高影;B:胸部局部SPECT显像,右侧乳腺区域可见显像剂分布增高影;C:CT定位像可见右侧乳腺类圆形软组织密度影;D:SPECT/CT融合显像,T/NT值为5.96;E:早期5 min SPECT静态显像,胸部右侧可见片状显像剂分布增高影;F:乳腺超声示右乳外上象限无回声区,呈毛刺征,BI-RADS 4c级;G:病理结果为右乳浸润性导管癌(苏木精-伊红染色,伊100);99Tcm-3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影术;BI-RADS:乳腺影像报告和数据系统。
Figure 2. 64 years old females with the breast integrin receptor imaging of 99Tcm-3PRGD2, ultrasonography of BI-RADS 4c and pathology
图 3 43岁女性患者乳腺99Tcm-3PRGD2整合素受体SPECT/CT显像图、超声BI-RADS 4b级声像图和病理图 图中,A:肘静脉注射99Tcm-3PRGD2 2 h行全身显像,于胸部左侧可见点状显像剂分布增高影;B:胸部局部SPECT显像,左侧乳腺区域可见显像剂分布增高影;C:CT定位像可见左侧乳腺类圆形软组织密度影;D:SPECT/CT融合显像,T/NT值为3.1;E:早期5 min SPECT静态显像,胸部未见明显显像剂分布增高影;F:乳腺超声示左乳外上象限无回声区,边界欠规整,BI -RADS 4b级;G:病理结果为左乳纤维腺瘤(苏木精-伊红染色,伊100);99Tcm-3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影;BI-RADS:乳腺影像报告和数据系统。
Figure 3. 43 years old females with the breast integrin receptor imaging of 99Tcm-3PRGD2, ultrasonography of BI-RADS 4b and pathology
表 1 56个乳腺占位病变病理类型与不同检查方法的诊断结果(个)
Table 1. Pathology classification of 56 breast lesions and the results of different inspection method(cases)
病理类型 病理检查 99Tcm-3PRGD2
SPECT/CT超声检查 阳性 阴性 阳性 阴性 浸润性导管癌 35 29 6 30 5 纤维腺瘤 14 0 14 7 7 乳腺腺病 2 2 0 0 2 乳腺增生伴腺瘤形成 3 2 1 0 3 脂肪坏死伴炎症反应 2 2 0 0 2 总计 56 35 21 37 19 注:表中,99Tcm-3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影术 表 2 99Tcm-3PRGD2 SPECT/CT显像与超声检查诊断效能的比较
Table 2. Comparation of the diagnostic efficiency of 99Tcm-3PRGD2 SPECT/CT imaging and ultrasonography
显像方法 灵敏度/% 特异度/% 准确率/% ROC曲线下面积 标准误 95%置信区间 下限 上限 超声检查 85.7 66.7 78.6a 0.76 0.07 0.62 0.90 99Tcm-3PRGD2 SPECT/CT 82.9 71.4 78.6a 0.77 0.07 0.63 0.91 超声检查+99Tcm-3PRGD2 SPECT/CT 94.3 90.5 92.9 0.92 0.04 0.84 1.00 注:表中,a:与超声检查+99Tcm-3PRGD2 SPECT联合显像比较,准确率的差异有统计学意义(χ2=77.17、74.87,均P < 0.05)。99Tcm- 3PRGD2:99Tcm-联胼尼克酰胺-3聚乙二醇-精氨酸-甘氨酸-天冬氨酸环肽二聚体;SPECT/CT:单光子发射计算机体层摄影术;ROC曲线:受试者工作特征曲线 -
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