Interrogating Glioma-Associated Microglia and Macrophage Dynamics Under CSF-1R Therapy with Multitracer In Vivo PET/MRI

• DOI: 10.2967/jnumed.121.263318
• Publication Date: 2022-02-03T21:05:19Z
• Authors: Claudia Foray; Cristina Barca; Alexandra Winkeler; Stefan Wagner; Sven Hermann; Michael Schäfers; Oliver M. Grauer; Bastian Zinnhardt; Andreas H. Jacobs
• Keywords: Translocator protein

<b>Background:</b> Glioma-associated microglia/macrophages (GAMM) are key players in creating an immunosuppressive microenvironment. They can be efficiently targeted by inhibiting the colony stimulating factor-1 receptor (CSF-1R). We employed non-invasive PET/CT-MRI using ¹⁸F-FET (amino-acid metabolism) and ¹⁸F-DPA-714 (translocator protein - TSPO) to (i) understand role of GAMM glioma initiation, (ii) monitor in-vivo therapy-induced depletion, (iii) observe repopulation after drug withdrawal. <b>Methods:</b> C57BL/6 mice (<i>n</i> = 44) orthotopically implanted with syngeneic mouse GL261 cells were treated different regimens PLX5622 (CSF-1R inhibitor) or vehicle, establishing a "preconditioning" "repopulation" model, respectively. Mice underwent longitudinal PET/CT-MR imaging. <b>Results:</b> The preconditioning model (PM) indicated similar tumor growth based on MRI (44.5 ± 24.8 %), ¹⁸F-FET- (18.3 11.3 %) ¹⁸F-DPA-714-PET (16 19.04 volume dynamics all groups, suggesting that not involved initiation. repopulation-model (RM) showed significantly reduced uptake (-45.6 18.4 together infiltration even repopulation, decreased (-54.29 8.6 as measured MRI, supported significant reduction (-50.2 5.3 %). <b>Conclusion:</b>¹⁸F-FET- ¹⁸F-DPA-714-PET/MRI allow assessment under various CSF-1R therapy. CSF-1R-mediated modulation may high interest (co-)therapy against glioma.