RT Journal Article
SR Electronic
T1 Interrogating Glioma-Associated Microglia and Macrophage Dynamics Under CSF-1R Therapy with Multitracer In Vivo PET/MRI
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1386
OP 1393
DO 10.2967/jnumed.121.263318
VO 63
IS 9
A1 Claudia Foray
A1 Cristina Barca
A1 Alexandra Winkeler
A1 Stefan Wagner
A1 Sven Hermann
A1 Michael Schäfers
A1 Oliver M. Grauer
A1 Bastian Zinnhardt
A1 Andreas H. Jacobs
YR 2022
UL http://jnm.snmjournals.org/content/63/9/1386.abstract
AB Glioma-associated microglia and macrophages (GAMMs) are key players in creating an immunosuppressive microenvironment. They can be efficiently targeted by inhibiting the colony-stimulating factor 1 receptor (CSF-1R). We applied noninvasive PET/CT and PET/MRI using 18F-fluoroethyltyrosine (18F-FET) (amino acid metabolism) and N,N-diethyl-2-[4-(2-18F-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (18F-DPA-714) (translocator protein) to understand the role of GAMMs in glioma initiation, monitor in vivo therapy-induced GAMM depletion, and observe GAMM repopulation after drug withdrawal. Methods: C57BL/6 mice (n = 44) orthotopically implanted with syngeneic mouse GL261 glioma cells were treated with different regimens using the CSF-1R inhibitor PLX5622 (6-fluoro-N-((5-fluoro-2-methoxypyridin-3-yl)methyl)-5-((5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)pyridin-2-amine) or vehicle, establishing a preconditioning model and a repopulation model, respectively. The mice underwent longitudinal PET/CT and PET/MRI. Results: The preconditioning model indicated similar tumor growth based on MRI (44.5% ± 24.8%), 18F-FET PET (18.3% ± 11.3%), and 18F-DPA-714 PET (16% ± 19.04%) volume dynamics in all groups, suggesting that GAMMs are not involved in glioma initiation. The repopulation model showed significantly reduced 18F-DPA-714 uptake (−45.6% ± 18.4%), significantly reduced GAMM infiltration even after repopulation, and a significantly decreased tumor volume (−54.29% ± 8.6%) with repopulation as measured by MRI, supported by a significant reduction in 18F-FET uptake (−50.2% ± 5.3%). Conclusion: 18F-FET and 18F-DPA-714 PET/MRI allow noninvasive assessment of glioma growth under various regimens of CSF-1R therapy. CSF-1R–mediated modulation of GAMMs may be of high interest as therapy or cotherapy against glioma.