新型靶向PD-L1的PET/CT分子探针评估非小细胞肺癌PD-L1表达及异质性的临床研究  

Novel PD-L1-targeted PET/CT molecular probe for evaluation of PD-L1 expression and tumor heterogeneity in non-small cell lung cancer

作　　者：赵亮 戴雅青 逄一臻 陈健豪 吴华[1] 孙龙[1] 林勤[2] 陈皓鋆[1] Zhao Liang;Dai Yaqing;Pang Yizhen;Chen Jianhao;Wu Hua;Sun Long;Lin Qin;Chen Haojun(Department of Nuclear Medicine&Minnan PET Center,the First Affiliated Hospital of Xiamen University,Xiamen 361003,China;Department of Radiation Oncology,the First Affiliated Hospital of Xiamen University,Xiamen 361003,China)

机构地区：[1]厦门大学附属第一医院核医学科及闽南PET中心,厦门361003 [2]厦门大学附属第一医院放射治疗科,厦门361003

出　　处：《中华核医学与分子影像杂志》2025年第3期133-137,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金(82071961,82422039)。

摘　　要：目的探讨68Ga标记靶向程序性死亡受体配体1(PD-L1)的新型PET/CT分子探针评估非小细胞肺癌(NSCLC)病灶PD-L1表达及异质性的可行性。方法前瞻性纳入2023年10月至2024年10月间在厦门大学附属第一医院新近确诊的NSCLC患者30例[男21例、女9例,年龄69(58,75)岁]。患者经静脉注射68Ga-1,4,7-三氮杂环壬烷-1,4,7-三乙酸(NOTA)-DK224后1 h进行PET/CT显像,计算SUV_(max)。对患者活组织检查(简称活检)样本进行免疫组织化学染色,计算PD-L1肿瘤阳性比例评分(TPS)。采用Mann-Whitney U检验比较2组间SUV_(max)差异。结果30例患者共获得活检样本31个,包括24个原发灶样本、1个淋巴结转移灶样本和6个内脏转移灶样本;16个TPS<1%,9个1%≤TPS<50%,6个TPS≥50%。PD-L1阳性肿瘤对68Ga-NOTA-DK224表现出良好的摄取。TPS≥1%的病灶SUV_(max)显著高于TPS<1%的[6.9(5.1,7.7)与3.8(3.1,4.2);Z=-4.47,P<0.001];TPS≥50%的病灶SUV_(max)显著高于TPS<50%的[8.6(7.3,12.4)与4.2(3.7,5.3);Z=-3.65,P<0.001]。30例患者中有24例存在多发转移灶,总共212个病灶,同一患者不同病灶间SUV_(max)存在高度异质性,中位倍数差异为2.3(范围:1.4~6.0),中位CV为28.3%(范围:11.7%~61.6%)。结论68Ga-NOTA-DK224 PET/CT显像能够准确、全面评估晚期NSCLC患者原发肿瘤和转移灶中PD-L1的表达及异质性情况。ObjectiveTo evaluate the feasibility of the novel programmed death-ligand 1(PD-L1)-targeted PET/CT molecular probe for evaluating PD-L1 expression and tumor heterogeneity in patients with non-small cell lung cancer(NSCLC).MethodsFrom October 2023 to October 2024,30 patients(21 males,9 females;age 69(58,75)years)with newly diagnosed NSCLC at the First Affiliated Hospital of Xiamen University were prospectively enrolled.All patients underwent PET/CT imaging 1 h after intravenous administration of 68Ga-1,4,7-triazacyclononane-1,4,7-triacetic acid(NOTA)-DK224,and SUV_(max) was calculated.Immunohistochemical staining on biopsy samples of patients were performed and the PD-L1 tumor proportion score(TPS)was calculated.The differences of SUV_(max) between two groups were compared by using Mann-Whitney U test.ResultsOf 30 patients,31 biopsy specimens were obtained including 24 primary lesion biopsies,1 lymph node lesion biopsy,and 6 metastatic lesion biopsies,with 16 TPS<1%,91%≤TPS<50%and 6 TPS≥50%.PD-L1-positive tumors showed relatively high uptake of 68Ga-NOTA-DK224.The SUV_(max) of TPS≥1%group was significantly higher than that of TPS<1%group(6.9(5.1,7.7)vs 3.8(3.1,4.2);Z=-4.47,P<0.001),and SUV_(max) of TPS≥50%group was significantly higher than that of TPS<50%group(8.6(7.3,12.4)vs 4.2(3.7,5.3);Z=-3.65,P<0.001).Of 30 patients,24 had multiple metastatic lesions with 212 lesions in total.The median fold difference was 2.3(range:1.4-6.0),and the median CV was 28.3%(range:11.7%-61.6%).Conclusion 68Ga-NOTA-DK224 PET/CT is able to accurately and comprehensively reflect PD-L1 expression and tumor heterogeneity in primary and metastatic NSCLC.

关 键 词：癌 非小细胞肺 抗原 CD274 同位素标记 镓放射性同位素 正电子发射断层显像术 体层摄影术 X线计算机 

分 类 号：R73[医药卫生—肿瘤]