From the ICO René Gauducheau, F-44800, Saint-Herblain, France.
Nantes Université, Univ Angers, CHU Nantes, INSERM, CNRS, CRCI2NA, F-44000, Nantes, France.
Clin Nucl Med. 2024 Aug 1;49(8):701-708. doi: 10.1097/RLU.0000000000005338. Epub 2024 Jun 20.
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.
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.
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).
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.
肿瘤相关巨噬细胞是三阴性乳腺癌（TNBC）的研究靶点。18kDa 转位蛋白（TSPO）是巨噬细胞的敏感标志物，在 TNBC 分层中有潜在的相关性。这项前瞻性研究（EITHICS，NCT04320030）旨在评估使用 18 F-DPA-714 的 TSPO PET/CT 成像在原发性 TNBC 中的潜力，与免疫组化、放射自显影和 TSPO 多态性进行比较。
纳入 13 例 TNBC 患者。他们接受了 TSPO 基因分型（HAB、MAB、LAB）、18 F-FDG PET/CT 和乳腺 MRI 检查。计算了半定量 PET 参数。在肿瘤病变、健康乳腺组织和胸肌上定义了 VOI，以获得 SUV、肿瘤与背景比（TBR）和时间-活性曲线（TAC）。此外，还进行了免疫组化、3 H-DPA-714 和 3 H-PK-11195 放射自显影。
大多数 TNBC 肿瘤（11/13，84%）具有 M2 极化巨噬细胞占优势，中位数比例为 82%（范围 44%-94%）。18 F-DPA-714 PET/CT 清楚地识别了 TNBC 肿瘤，TBR 良好。根据肌肉背景，18 F-DPA-714 TAC 分为“高于肌肉”、“等于肌肉”和“低于肌肉”三种不同的模式。对于“高于肌肉”组（2 例 HAB 和 2 例 MAB）、“等于肌肉”组（3 例 HAB、3 例 MAB 和 1 例 LAB）和“低于肌肉”组（1 例 LAB 和 1 例 MAB），肿瘤 TAC 显示 18 F-DPA-714 积聚斜率分别为 1.35、0.62 和 0.22，SUV 平均值中位数分别为 4.02（2.09-5.31）、1.66（0.93-3.07）和 0.61（0.43-1.02）。
本研究成功地证明了 18 F-DPA-714 对 TNBC 肿瘤的靶向作用，TBR 良好，能够对 TSPO 多态性状态可能影响的摄取模式进行分层。应在更大的人群中进行进一步的研究，以评估这种新生物标志物的预后价值。
