Pilot study with [18F]DPA-714 PET-CT to explore tumor-associated-macrophages in triple negative breast cancer.
Authors: Rousseau Caroline , Arlicot Nicolas , Campion Loic , Kerdraon Olivier , Ferrer Ludovic , Vercouillie Johnny , Ouldamer Lobna , Doutriaux-Dumoulin Isabelle , Boiffard Florence , Renaudeau Céline , Mouton Alexis , Chalon Sylvie , Gulhan Zuhal , Fleury Vincent , Le Thiec Maelle , Maucherat Bruno , Rusu Daniela , Allam Nadia , Santiago-Ribeiro Maria-Joao , Kraeber-Bodere Francoise 
Published: June 2022

e12557

Background: Triple-negative breast cancer (TNBC) tends to exhibit aggressive behavior lacking from targeted therapies. Tumor-associated-macrophages (TAMs as M2 and M1 macrophages) are interest targets in TNBC to approach the tumor patient immunity. The mitochondrial translocator protein (TSPO), a sensitive marker for macrophages, could be interesting for TNBC micro-environment stratification. We performed a multicenter imaging pilot study (NCT04320030) using non-invasive [18F]DPA-714 (DPA), a TSPO PET radioligand, aiming at assessing immunity to define the immunotherapy possibilities in TNBC patients. Methods: All patients underwent TSPO genotyping (LAB: Low Affinity Binder, MAB: Mixed and HAB: High), [18F]FDG (FDG) and DPA PET-CT, macrophages immunochemistry and in vitro TSPO autoradiography using both tritiated PK11195 (PK) and DPA. Thorax PET-CT was acquired just after injection (DPA1) to 30 min, then from 45 min (DPA2) to 60 min, followed by a whole body PET-CT. Groups of interest (Macrophages immunochemistry and Genotype) were compared using Kruskal-Wallis test. Correlation between continuous parameters were determined using Spearman’s Rho. Results: A total of 13 TNBC patients were included. No adverse events occurred after DPA injection. For TSPO genotyping, 2/13 (15.5%) patients were LAB, 6/13 (46%) MAB and 5/13 (38.5%) HAB. All of them showed FDG and DPA uptake regardless of the patient's genotype without significant difference between the 3 groups. The DPA kinetics showed a tracer accumulation between DPA1 and DPA2, whatever patient genotypes, observed on SUVmax (p = 0.0015), SUVmean (p = 0.0015) and TL-DPA (p = 0.0024). A correlation between FDG and DPA1 either DPA2 tumor volume was shown, respectively (p = 0.0252 and 0.0067) as well as between the TLG (FDG) and the TL-DPA1 (p = 0.0346) regardless of the patient's genotype. Macrophages immunochemistry showed a tendency difference for M2 percentage (p = 0.09) between the 3 genotypes groups. In vitro binding ratio (PK/DPA), measured for both radioligands, on adjacent tumor slices, was 1.77 (1.35-2.21). A difference in this binding ratio was observed between MAB and HAB (Mean 1.68±0.36) compared to LAB 3.04±0.23 (p = 0.0367), suggesting that DPA binding is sensitive to TSPO genotype, unlike PK binding. Conclusions: Despite the limited population, all TNBC tumor patients were DPA positive with an accumulation over time. The total glycolysis and total DPA uptake in the tumor were correlated, which may link tumor aggressiveness and DPA uptake. These data were confirmed by a better sensitivity for HAB and MAB vs LAB. DPA seemed to be a promising tracer to explore non-invasively TNBC patient’s immunity. Clinical trial information: NCT04320030.