{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:46:33Z","timestamp":1788911193754,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Macrophages can promote tumor development. Preclinically, targeting macrophages by colony-stimulating factor 1 (CSF1)\/CSF1 receptor (CSF1R) monoclonal antibodies (mAbs) enhances conventional therapeutics in combination treatments. The physiological distribution and tumor uptake of CSF1R mAbs are unknown. Therefore, we radiolabeled a murine CSF1R mAb and preclinically visualized its biodistribution by PET. CSF1R mAb was conjugated to <jats:italic>N<\/jats:italic>-succinyl-desferrioxamine (<jats:italic>N<\/jats:italic>-suc-DFO) and subsequently radiolabeled with zirconium-89 (<jats:sup>89<\/jats:sup>Zr). Optimal protein antibody dose was first determined in non-tumor-bearing mice to assess physiological distribution. Next, biodistribution of optimal protein dose and <jats:sup>89<\/jats:sup>Zr-labeled isotype control was compared with PET and <jats:italic>ex vivo<\/jats:italic> biodistribution after 24 and 72 h in mammary tumor-bearing mice. Tissue autoradiography and immunohistochemistry determined radioactivity distribution and tissue macrophage presence, respectively. [<jats:sup>89<\/jats:sup>Zr]Zr-DFO-<jats:italic>N<\/jats:italic>-suc-CSF1R-mAb optimal protein dose was 10 mg\/kg, with blood pool levels of 10 \u00b1 2% injected dose per gram tissue (ID\/g) and spleen and liver uptake of 17 \u00b1 4 and 11 \u00b1 4%ID\/g at 72 h. In contrast, 0.4 mg\/kg of [<jats:sup>89<\/jats:sup>Zr]Zr-DFO-<jats:italic>N<\/jats:italic>-suc-CSF1R mAb was eliminated from circulation within 24 h; spleen and liver uptake was 126 \u00b1 44% and 34 \u00b1 7%ID\/g, respectively. Tumor-bearing mice showed higher uptake of [<jats:sup>89<\/jats:sup>Zr]Zr-DFO-<jats:italic>N<\/jats:italic>-suc-CSF1R-mAb in the liver, lymphoid tissues, duodenum, and ileum, but not in the tumor than did <jats:sup>89<\/jats:sup>Zr-labeled control at 72 h. Immunohistochemistry and autoradiography showed that <jats:sup>89<\/jats:sup>Zr was localized to macrophages within lymphoid tissues. Following [<jats:sup>89<\/jats:sup>Zr]Zr-DFO-<jats:italic>N<\/jats:italic>-suc-CSF1R-mAb administration, tumor macrophages were almost absent, whereas isotype-group tumors contained over 500 cells\/mm<jats:sup>2<\/jats:sup>. We hypothesize that intratumoral macrophage depletion by [<jats:sup>89<\/jats:sup>Zr]Zr-DFO-<jats:italic>N<\/jats:italic>-suc-CSF1R-mAb precluded tumor uptake higher than <jats:sup>89<\/jats:sup>Zr-labeled control. Translation of molecular imaging of macrophage-targeting therapeutics to humans may support macrophage-directed therapeutic development.<\/jats:p>","DOI":"10.3389\/fonc.2021.786191","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T13:28:40Z","timestamp":1641302920000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Radiolabeled Monoclonal Antibody Against Colony-Stimulating Factor 1 Receptor Specifically Distributes to the Spleen and Liver in Immunocompetent Mice"],"prefix":"10.3389","volume":"11","author":[{"given":"Stijn J. 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