正常乳腺与乳腺癌病灶的^18F-阿法肽PET/CT显像特征

Characteristics of ^18F-Alfatide Ⅱ PET/CT imaging in normal breast and malignant breast cancer

目的探讨正常乳腺组织和乳腺癌^18F-阿法肽(Alfatide Ⅱ) PET/CT显像的特点。方法前瞻性纳入2016年3月至2017年8月间22例怀疑乳腺恶性结节或肿块的女性患者,年龄(52±10)岁,均于穿刺活组织检查和术前行^18F-Alfatide Ⅱ PET/CT显像,视觉分析正常乳腺的显像特点,并对比患者正常乳腺与子宫(按有/无绝经分组)及乳腺癌病灶最大标准摄取值(SUVmax)的差异。根据病灶的放射性摄取分布形态特点将病灶进行分型,通过免疫组织化学检查和荧光原位杂交检测判定其分子亚型,分析不同分型和分子亚型病灶的SUVmax。采用两样本t检验和Pearson或Spearman相关分析处理数据。结果22例患者有23个癌变乳腺(1例双侧乳腺癌病灶,1例一侧乳腺切除);20个正常乳腺和21个正常子宫(1例因子宫肌瘤切除),随访1年以上均未发现恶性病变。^18F-Alfatide Ⅱ PET/CT显像示11个正常乳腺可见腺体边缘部结缔组织区条索状放射性摄取轻度增高,SUVmax高于中心区腺体组织(1.81±0.67与0.79±0.37;t=6.771,P<0.001);此11例中,除1例子宫切除外,余10例均伴子宫弥漫性放射性摄取增高。19例患者正常乳腺结缔组织SUVmax (1.31±0.80)和子宫SUVmax(3.80±1.79)呈正相关(r=0.785,P<0.05)。将22例患者分为未绝经组和绝经组,2组正常乳腺结缔组织SUVmax(1.81±0.67与0.72±0.39)及子宫SUVmax(5.11±1.06与2.04±0.39)差异均有统计学意义(t值:4.42和8.66,均P<0.01)。23个乳腺癌病变均有不同程度的放射性摄取增高,SUVmax为6.93±3.97,明显高于正常乳腺乳头区、结缔组织区及腺体区的SUVmax(t值:6.784~7.559,均P<0.05)。根据放射性摄取分布形态分为肿块型5个、结节型3个、弥漫型4个、多灶/多中心型11个,以多灶/多中心型灶SUVmax最高(F=3.55,P<0.05)。4个分子分型中基底样型乳腺癌病灶SUVmax较低(2.49±1.67);人表皮生长因子受体2(HER2)表达水平高的病灶SUVmax高。结论^18F-Alfatide Ⅱ PET/CT显像示正常乳腺有轻度的放射性分布,主要集中于乳头区和腺体边缘的结缔组织区域,且与子宫的放射性摄取程度呈正相关。乳腺癌病灶的放射性摄取程度明显高于正常乳腺。不同形态特点的乳腺癌病灶均有明显的放射性摄取,以多灶/多中心型最高。不同分子亚型的乳腺癌病灶放射性摄取程度不同,基底样型乳腺癌病灶的放射性摄取程度较低;HER2表达水平较高的病灶SUVmax较高。

Objective To investigate the characteristics of ^18F-Alfatide Ⅱ PET/CT imaging in normal breasts and breast cancer lesions. Methods From March 2016 to August 2017, 22 female patients (age:(52±10) years) with suspected breast malignant nodules or masses were prospectively enrolled. All patients underwent ^18F-Alfatide Ⅱ PET/CT imaging prior to biopsy or surgery. The imaging characteristics of normal breasts were assessed visually and the difference of maximum standardized uptake value (SUVmax) in normal breasts and uterus between patients with and without menopause was compared, SUVmax of cancer lesions and normal breasts was also compared. Breast cancer lesions were classified according to the distribution characteristics of radioactive uptake, and molecular subtypes were determined by immunohistochemistry and fluorescence in situ hybridization. The SUVmax of different morphological and molecular subtypes were analyzed. Two-sample t test and Pearson or Spearman correlation analysis were used to analyze the data. Results There were 23 breast cancer lesions (one patient had bilateral breast cancer lesions and one had a history of one-side breast resection), 20 normal breasts and 21 normal uteruses. Those normal breasts and uteruses didn′t show any malignant change after being followed up for more than 1 year (one patient had uterine fibroids resection). There was a slight increase of radioactivity uptake in the cord-like connective tissue region at the margin of the gland in 11 mammary glands, and the SUVmax was higher than that of glandular tissue in the central region (1.81±0.67 vs 0.79±0.37;t=6.771, P<0.001). Of the 11 cases, except for one patient whose uterus was removed, the other 10 patients were accompanied by increased diffuse radioactivity of the uterus. SUVmax of 19 normal breast connective tissues (1.31±0.80) and uterus (3.80+ 1.79) were positively correlated (r=0.785, P<0.05). For patients with/without menopause (n=11 each group), the SUVmax of normal breast connective tissues (0.72±0.39 vs 1.81±0.67) and uterus (2.04±0.39 vs 5.11±1.06) were significantly different (t values: 4.42 and 8.66, both P<0.01). Different levels of radioactive uptake were observed in all 23 breast cancer lesions, with SUVmax of 6.93±3.97, which was significantly higher than the nipple, connective tissue and glandular tissue of normal breasts (t values: 6.784-7.559, all P<0.05). According to the characteristics of the radioactivity uptake distribution of the lesion, among the 23 breast cancer lesions, 5 were mass type, 3 were nodular type, 4 were diffuse type, and 11 were multi-focal/multi-center type, and the SUVmax of multi-focal/multi-center type was the highest (F=3.55, P<0.05). The SUVmax of basal-like breast cancer lesions (2.49±1.67) was lower than the other three molecular subtypes. Lesions with high level human epidermal growth factor receptor 2 (HER2) positive expression had higher SUVmax. Conclusions ^18F-Alfatide Ⅱ PET/CT imaging shows that normal breasts have a slight radioactive distribution, mainly concentrate in the nipple and connective tissues around the glandular, and the uptake have a positive correlation with the radioactive uptake of the uterus. The degree of radioactive uptake of breast cancer lesions is significantly higher than that of normal breasts. Breast cancer lesions with different morphological features all have obvious radioactive uptake, especially the multi-focal/multi-center type. Different molecular subtypes have different radioactive uptake levels. SUVmax is lower in basal-like breast cancer lesions, and higher in HER2 positive expression lesions.