Pilot Feasibility Study

Abstract

Abstract 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 18F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism. Patients and Methods Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18F-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, 3H-DPA-714, and 3H-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%). 18F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18F-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 18F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUVmean 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 18F-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.