趋化因子受体4靶向探针68Ga-NOTA-NFBPET/CT显像在乳腺癌中的应用

68Ga-NOTA-NFB PET/CT imaging in breast cancer: clinical study of a new targeted agent for chemokine receptor 4

目的探讨趋化因子受体4(CXCR4)靶向探针68Ga-1,4,7-三氮杂环壬烷-1,4,7-三乙酸-TN1400E(NOTA-NFB) PET/CT显像用于乳腺癌的可行性及显像和病理的关系。方法2014年6月至12月间11例女性乳腺癌患者(年龄38~68岁)均于新辅助化疗后手术,病理确认为乳腺浸润性癌(非特殊型)。所有患者于新辅助化疗前行68Ga-NOTA-NFB和18F-脱氧葡萄糖(FDG) PET/CT显像。3例于4个化疗周期后再次行68Ga-NOTA-NFB PET/CT显像。用感兴趣区(R0I)法测量病灶最大标准摄取值(SUVmax),并计算肿瘤/正常组织放射性(T/NT)比值。采用配对I检验及Spearman相关分析对数据进行处理。结果新辅助化疗前68Ga-NOTA-NFB显像与18F-FDG显像比较,原发灶SUVmax差异有统计学意义(3.78+2.03与8.11±5.14;t=-3.01,P<0.05),而T/NT比值间差异无统计学意义(9.36±7.81 和 15.62± 14.51;t=-1.63,P>0.05);淋巴结转移灶 SUVmax间差异无统计学意义(t=-2.02,P>0.05),而T/NT间差异有统计学意义(t=-2.43,P<0.05)。3例患者新辅助化疗后68Ga-NOTA-NFB显像示T/NT降低。68Ga-NOTA-NFB的T/NT与细胞增殖核抗原(Ki-67)之间无相关性(rs=0.600/=0.051)。结论68Ga-NOTA-NFB PET/CT显像可以用于乳腺癌,为CXCR4的显像评价提供了新方法,并且在新辅助化疗效果评价中可能有应用价值。

Objective To investigate the clinical application of chemokine receptor 4 (CXCR4)-targeted PET/CT imaging in breast cancer using 68Ga-1,4,7-triazacyclononane-l, 4,7-triacetic acid-TN 14003 (NOTA-NFB) and the correlation between 68Ga-NOTA-NFB uptake and pathology. Methods From June 2014 to December 2014, 11 female patients (age range: 38-68 years) with non-specific invasive breast cancer were recruited in this study. All patients underwent neoadjuvant chemotherapy before surgery.68Ga-NOTA-NFB and 18F-fluorodeoxyglucose (FDG) PET/CT imaging were performed before the chemotherapy. Three patients also underwent 68Ga-NOTA-NFB PET/CT imaging after the fourth cycle of chemotherapy. The region of interest (ROI) method was used to measure the maximum standardized value (SUVmax) and tumor/non-tumor (T/NT) ratio was calculated. Paired t test and Spearman correlation analysis were used for statistical analysis.Results The SUVmax values of primary lesions were 3.78±2.03 and 8.11±5.14 (t=-3.01, P<0.05) respectively in 68Ga-NOTA-NFB imaging and 18F-FDG imaging.The T/NT ratios for primary lesions were not significantly different between the two imaging methods (9.36±7.81 vs 15.62±14.51;Z=-1.63 , P>0. 05). In the metastatic lymph nodes, SUVmax values were not significantly different between 68Ga-NOTA-NFB imaging and 18F-FDG imaging(Z=-2.O2, P〉0.05), but T/NT ratios were significantly different (t=-2.43, P<0. 05). After neoadjuvant chemotherapy, T/NT ratios were decreased in the 3 patients. Correia tion was not found between T/NT in 68Ga-NOTA-NFB imaging and Ki-67, but the P value was close to 0.05 (rs=0.600, P=0.051). Conclusion 68Ga-NOTA-NFB PET/CT can be used as a new CXCR4-targered imaging in diagnosis of breast cancer, and it may be beneficial to evaluate the effect of neoadjuvant chemotherapy.