正电子发射体层成像/磁共振双探针显像在胰腺神经内分泌肿瘤分级诊断中的价值

The value of dual probes in tracerpositron emission tomography/magnetic resonance imaging in the grading diagnosis of pancreatic neuroendocrine neoplasms

目的探讨^(68)Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽(^(68)Ga-DOTA-TATE)联合^(18)F-氟代脱氧葡萄糖(^(18)F-FDG)正电子发射体层成像/磁共振(PET/MR)双探针多参数显像在胰腺神经内分泌肿瘤(PNEN)诊断和分级方面的价值。方法回顾性分析上海交通大学医学院附属瑞金医院2020年4月9日至2022年2月24日经穿刺或手术病理证实的59例胰腺占位患者[男27例、女32例,年龄22~75岁(51.8±13.3)岁]的临床资料,以及^(68)Ga-DOTA-TATE PET/MR和^(18)F-FDG PET/MR显像资料和参数。将所有病例分为PNEN组(42例)和非PNEN组(17例);其中39例胰腺神经内分泌瘤(PNET)患者进一步分为1级组(27例)、2级组(12例)。通过最小绝对收缩和选择算子逻辑回归方法选择非零参数,将选定的特征与相应的非零系数结合构建逻辑回归模型。呈偏态分布的计量资料采用Mann-Whitney U检验比较。采用受试者操作特征曲线确定最佳临界值,评估诊断效能。结果与非PNEN组相比,PNEN组患者病灶^(68)Ga-DOTA-TATE最大标准摄取值[46.70(22.37,76.35)比7.12(4.75,8.64)]、平均标准摄取值[25.50(13.^(18),43.90)比3.65(2.89,4.69)]、标准摄取值峰值[27.17(12.39,46.97)比5.46(4.12,6.56)],病灶总生长抑素受体表达[^(68).21(32.52,440.96)比26.02(14.87,69.57)],^(68)Ga-DOTA-TATE/^(18)F-FDG最大标准摄取值[12.71(3.80,21.70)比1.10(0.52,2.35)],^(68)Ga-DOTA-TATE肿瘤背景比[13.31(5.54,22.38)比1.57(1.31,2.66)]、肿瘤肝脏比[6.54(2.90,9.63)比0.74(0.65,0.94)]、肿瘤脾脏比[2.36(0.97,3.70)比0.25(0.23,0.38)]、肿瘤纵隔比[104.41(34.03,206.52)比16.00(12.87,21.46)],^(68)Ga-DOTA-TATE最大标准摄取值/最小表观弥散系数(ADCmin)[55.14(22.50,96.37)比6.76(4.39,12.76)],^(68)Ga-DOTA-TATE平均标准摄取值/ADCmin[34.57(13.47,55.13)比3.57(2.46,6.81)]增高,差异均有统计学意义(U=28.00、25.00、32.00、198.00、54.00、31.00、28.00、19.00、10.00、56.00、44.00,均P<0.01)。PET/MR双探针显像诊断PNEN与非PNEN的曲线下面积(AUC)和准确率分别为0.941和96.6%。模型Y1诊断PNEN的AUC和准确率分别为0.959和96.6%。模型Y1与PET/MR双探针显像诊断PNEN的AUC比较差异无统计学意义(P>0.05),但结合模型Y1能提高诊断PNEN的准确率(100.0%)。与PNET 1级相比,PNET 2级的肿瘤最大径[2.69 cm(2.08 cm,5.00 cm)比1.50 cm(1.20 cm,2.50 cm)]、肿瘤代谢体积[7.56 mL(4.45 mL,53.57 mL)比2.16 mL(1.22 mL,5.48 mL)、病灶总糖酵解[22.24(11.95,^(18)9.85)比3.81(2.11,^(18).67)]、^(18)F-FDG肿瘤背景比[2.94(2.00,3.96)比1.48(1.29,3.72)]、^(18)F-FDG肿瘤肝脏比[2.32(1.35,2.98)比1.08(0.90,2.17)]、生长抑素受体表达体积[8.00(3.06,40.00)比1.91(0.95,4.88)]增高,差异均有统计学意义(U=66.00、66.00、77.00、93.00、90.00、65.50,均P<0.05)。肿瘤最大径是鉴别PNET 2级与1级的最佳单项参数,其AUC为0.796,最佳临界值为1.90 cm。包含肿瘤最大径和^(68)Ga-DOTA-TATE肿瘤背景比的模型Y2鉴别2级与1级的AUC为0.835。肿瘤最大径与模型Y2的AUC比较差异无统计学意义(P>0.05),但肿瘤最大径结合模型Y2能提高鉴别2级与1级的准确率(94.9%)。结论^(68)Ga-DOTA-TATE联合^(18)F-FDG PET/MR双探针多参数显像能够提高PNEN诊断和分级的准确率,有助于患者临床治疗方式的选择。

Objective To explore the diagnostic and grading value of combination of^(68)Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide(^(68)Ga-DOTA-TATE)and^(18)F-flurodeoxyglucose(^(18)F-FDG)dual probes in multi-parameter positron emission tomography(PET)/magnetic resonance(MR)imaging in pancreatic neuroendocrine neoplasm(PNEN).Methods From April 9th,2020 to February 24th,2022,in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,the clinical data and the imaging of^(68)Ga-DOTA-TATE PET/MR and^(18)F-FDG PET/MR of 59 patients with pancreatic tumors(27 male,32 female,aged 22 to 75 years old(51.8±13.3)years old),confirmed by surgical or biopsy pathology were retrospectively analyzed.All the cases were divided into PNEN group(42 cases)and non-PNEN group(17 cases)according to pathological results.Among which 39 patients with PNET were further divided into grade 1 group(G1 group,27 cases)and grade 2 group(G2 group,12 cases).Non-zero parameters were selected via the least absolute shrinkage and selection operator(LASSO)regression approach,and a logistic regression model was established by combination of the selected features and the corresponding non-zero coefficients.The measurement data with non-normal distribution were compared by Mann-Whitney U test.The receiver operating characteristic(ROC)curve were used to detemine the optimal cut off value to assess the dignostic efficiency.Results Compared with those of non-PNEN group,the parameters of PNEN group increased,which included maximum standard uptake value of^(68)Ga-DOTA-TATE(SUVGmax,46.70(22.37,76.35)vs.7.12(4.75,8.64)),mean standard uptake value of^(68)Ga-DOTA-TATE(SUVGmean,25.50(13.^(18),43.90)vs.3.65(2.89,4.69)),peak standard uptake value of^(68)Ga-DOTA-TATE(SUVGpeak,27.17(12.39,46.97)vs.5.46(4.12,6.56)),total lesion somatostatin receptor(SSR)expression(TLSRE,^(68).21(32.52,440.96)vs.26.02(14.87,69.57)),SUVGmax/maximum standard uptake value of^(18)F-FDG(SUVFmax,12.71(3.80,21.70)vs.1.10(0.52,2.35)),tumor to background ratio of^(68)Ga-DOTA-TATE(TBRG,13.31(5.54,22.38)vs.1.57(1.31,2.66)),tumor to liver ratio of^(68)Ga-DOTA-TATE(T/LG,6.54(2.90,9.63)vs.0.74(0.65,0.94)),tumor to spleen ratio of^(68)Ga-DOTA-TATE(T/SG,2.36(0.97,3.70)vs.0.25(0.23,0.38)),tumor to mediastinum ratio of^(68)Ga-DOTA-TATE(T/MG,104.41(34.03,206.52)vs.16.00(12.87,21.46)),SUVGmax/minimum apparent diffusion coeffecient(ADCmin,55.14(22.50,96.37)vs.6.76(4.39,12.76))and SUVGmean/ADCmin(34.57(13.47,55.13)vs.3.57(2.46,6.81)),and the differences were statistically significant(U=28.00,25.00,32.00,198.00,54.00,31.00,28.00,19.00,10.00,56.00 and 44.00,all P<0.01).The area under the curve(AUC)and diagnostic accuracy of dual-probe PET/MR imaging in the diagnosis of PNEN and non-PNEN were 0.941 and 96.6%,respectively.The AUC and diagnostic accuracy of model Y1 in the diagnosis of PNEN and non-PNEN were 0.959 and 96.6%,respectively.There was no significant difference in AUC between model Y1 and dual-probe PET/MR imaging in PNEN diagnosis(P>0.05),however combining model Y1 could improve the accuracy of PNEN diagnosis(100.0%).Compared with those of PNET G1 group,the parameters of G2 Group were higher,which included the maximum diameter of tumor(2.69 cm(2.08 cm,5.00 cm)vs.1.50 cm(1.20 cm,2.50 cm)),metabolic tumor volume(MTV,7.56 mL(4.45 mL,53.57 mL)vs.2.16 mL(1.22 mL,5.48 mL)),total lesion glycolysis(TLG,22.24(11.95,^(18)9.85)vs.3.81(2.11,^(18).67)),tumor to background ratio of^(18)F-FDG(TBRF,2.94(2.00,3.96)vs.1.48(1.29,3.72)),tumor to liver ratio of^(18)F-FDG(T/LF,2.32(1.35,2.98)vs.1.08(0.90,2.17))and SSR-expressing tumor volume(SRETV,8.00(3.06,40.00)vs.1.91(0.95,4.88)),and the differences were statistically significant(U=66.00、66.00、77.00、93.00、90.00、65.50,all P<0.05).The maximum diameter of tumor was the best single parameter for the differential diagnosis of PNET G2 and G1,AUC was 0.796 and the cutoff value was 1.90 cm.The model Y2,which combined the maximum diameter of tumor and TBRG had an AUC of 0.835 for the differential diagnosis of PNET G2 and G1.There was no significant difference in AUC between the maximum diameter of tumor and model Y2(P>0.05).However the combination of the maximum diameter of tumor and model Y2 could improve the accuracy of differential diagnosis of PNET G2 and G1(94.87%).Conclusion The combination of multi-parameter of^(68)Ga-DOTA-TATE and dual-probe^(18)F-FDG PET/MR imaging can improve the diagnostic and grading accuracy of PNEN,which may be helpful in the selection of clinical treatment for patients.