Abstract：
UNASSIGNED: Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18 F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism.
METHODS: Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18 F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3 H-DPA-714, and 3 H-PK-11195 autoradiography were conducted.
RESULTS: The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%-94%). 18 F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18 F-DPA-714 TACs were identified, categorized as \"above muscular,\" \"equal to muscular,\" and \"below muscular\" with reference to the muscular background. For the \"above muscular\" group (2 HAB and 2 MAB), \"equal muscular\" group (3 HAB, 3 MAB, and 1 LAB), and \"below muscular\" group (1 LAB and 1 MAB), tumor TACs showed a 18 F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUV mean of 4.02 (2.09-5.31), 1.66 (0.93-3.07), and 0.61 (0.43-1.02).
CONCLUSIONS: This study successfully demonstrated TNBC tumor targeting by 18 F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker.
METHODS: Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18 F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3 H-DPA-714, and 3 H-PK-11195 autoradiography were conducted.
RESULTS: The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%-94%). 18 F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18 F-DPA-714 TACs were identified, categorized as \"above muscular,\" \"equal to muscular,\" and \"below muscular\" with reference to the muscular background. For the \"above muscular\" group (2 HAB and 2 MAB), \"equal muscular\" group (3 HAB, 3 MAB, and 1 LAB), and \"below muscular\" group (1 LAB and 1 MAB), tumor TACs showed a 18 F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUV mean of 4.02 (2.09-5.31), 1.66 (0.93-3.07), and 0.61 (0.43-1.02).
CONCLUSIONS: This study successfully demonstrated TNBC tumor targeting by 18 F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker.
摘要：
肿瘤相关巨噬细胞是三阴性乳腺癌（TNBC）的目标。易位体蛋白18kDa(TSPO)是巨噬细胞的敏感标记,并且在TNBC分层中具有潜在的相关性。这项试点前瞻性研究(EITHICS，NCT04320030）旨在评估使用18F-DPA-714在原发性TNBC中进行TSPOPET/CT成像的潜力，与免疫组织化学相比，放射自显影,和TSPO多态性。
方法：纳入13例TNBC患者。他们接受了TSPO基因分型(HAB，MAB,实验室),18F-FDGPET/CT,和乳房MRI。计算半定量PET参数。VOIs是在肿瘤病变上定义的，健康的乳房组织,和胸肌来获得SUV，肿瘤背景比（TBR），和时间-活动曲线(TACs)。此外,免疫组织化学，进行3H-DPA-714和3H-PK-11195放射自显影。
结果：大多数TNBC肿瘤（11/13，84％）具有M2极化巨噬细胞的优势，中位数比例为82％（范围，44%-94%）。18F-DPA-714PET/CT清楚地鉴定了TBR优异的TNBC肿瘤。确定了三种不同的18F-DPA-714TACs模式，归类为“以上肌肉，“\”等于肌肉，\"和\"下面的肌肉\"参照肌肉背景。对于“以上肌肉”组（2HAB和2MAB），“相等肌肉”组(3HAB，3MAB,和1个实验室），和“低于肌肉”组(1个LAB和1个MAB)，肿瘤TACs显示18F-DPA-714积累斜率分别为1.35、0.62和0.22，SUVmean中位数为4.02（2.09-5.31），1.66(0.93-3.07),和0.61（0.43-1.02）。
结论：这项研究成功地证明了18F-DPA-714对TNBC肿瘤的靶向性，允许对3种可能受TSPO多态性状态影响的摄取模式进行分层。应该在更大的人群中进行进一步的研究，以评估这种新的生物标志物的预后价值。
方法：纳入13例TNBC患者。他们接受了TSPO基因分型(HAB，MAB,实验室),18F-FDGPET/CT,和乳房MRI。计算半定量PET参数。VOIs是在肿瘤病变上定义的，健康的乳房组织,和胸肌来获得SUV，肿瘤背景比（TBR），和时间-活动曲线(TACs)。此外,免疫组织化学，进行3H-DPA-714和3H-PK-11195放射自显影。
结果：大多数TNBC肿瘤（11/13，84％）具有M2极化巨噬细胞的优势，中位数比例为82％（范围，44%-94%）。18F-DPA-714PET/CT清楚地鉴定了TBR优异的TNBC肿瘤。确定了三种不同的18F-DPA-714TACs模式，归类为“以上肌肉，“\”等于肌肉，\"和\"下面的肌肉\"参照肌肉背景。对于“以上肌肉”组（2HAB和2MAB），“相等肌肉”组(3HAB，3MAB,和1个实验室），和“低于肌肉”组(1个LAB和1个MAB)，肿瘤TACs显示18F-DPA-714积累斜率分别为1.35、0.62和0.22，SUVmean中位数为4.02（2.09-5.31），1.66(0.93-3.07),和0.61（0.43-1.02）。
结论：这项研究成功地证明了18F-DPA-714对TNBC肿瘤的靶向性，允许对3种可能受TSPO多态性状态影响的摄取模式进行分层。应该在更大的人群中进行进一步的研究，以评估这种新的生物标志物的预后价值。
