دورية أكاديمية
Radiolabeled Monoclonal Antibody Against Colony-Stimulating Factor 1 Receptor Specifically Distributes to the Spleen and Liver in Immunocompetent Mice
| العنوان: | Radiolabeled Monoclonal Antibody Against Colony-Stimulating Factor 1 Receptor Specifically Distributes to the Spleen and Liver in Immunocompetent Mice |
|---|---|
| المؤلفون: | Stijn J. H. Waaijer, Frans V. Suurs, Cheei-Sing Hau, Kim Vrijland, Karin E. de Visser, Derk Jan A. de Groot, Elisabeth G. E. de Vries, Marjolijn N. Lub-de Hooge, Carolina P. Schröder |
| المصدر: | Frontiers in Oncology, Vol 11 (2021) |
| بيانات النشر: | Frontiers Media S.A. |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | positron emission tomography (PET), antibody immunotherapy, noninvasive imaging in animal models, pharmacokinetics/pharmacodynamics (PKPD), tumor-associated macrophage (TAM), Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | 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 N-succinyl-desferrioxamine (N-suc-DFO) and subsequently radiolabeled with zirconium-89 (89Zr). Optimal protein antibody dose was first determined in non-tumor-bearing mice to assess physiological distribution. Next, biodistribution of optimal protein dose and 89Zr-labeled isotype control was compared with PET and ex vivo biodistribution after 24 and 72 h in mammary tumor-bearing mice. Tissue autoradiography and immunohistochemistry determined radioactivity distribution and tissue macrophage presence, respectively. [89Zr]Zr-DFO-N-suc-CSF1R-mAb optimal protein dose was 10 mg/kg, with blood pool levels of 10 ± 2% injected dose per gram tissue (ID/g) and spleen and liver uptake of 17 ± 4 and 11 ± 4%ID/g at 72 h. In contrast, 0.4 mg/kg of [89Zr]Zr-DFO-N-suc-CSF1R mAb was eliminated from circulation within 24 h; spleen and liver uptake was 126 ± 44% and 34 ± 7%ID/g, respectively. Tumor-bearing mice showed higher uptake of [89Zr]Zr-DFO-N-suc-CSF1R-mAb in the liver, lymphoid tissues, duodenum, and ileum, but not in the tumor than did 89Zr-labeled control at 72 h. Immunohistochemistry and autoradiography showed that 89Zr was localized to macrophages within lymphoid tissues. Following [89Zr]Zr-DFO-N-suc-CSF1R-mAb administration, tumor macrophages were almost absent, whereas isotype-group tumors contained over 500 cells/mm2. We hypothesize that intratumoral macrophage depletion by [89Zr]Zr-DFO-N-suc-CSF1R-mAb precluded tumor uptake higher than 89Zr-labeled control. Translation of molecular imaging of macrophage-targeting therapeutics to humans may support macrophage-directed therapeutic ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2234-943X |
| العلاقة: | https://www.frontiersin.org/articles/10.3389/fonc.2021.786191/fullTest; https://doaj.org/toc/2234-943XTest; https://doaj.org/article/8ac7559f52274598852b4ce0df5c1d1fTest |
| DOI: | 10.3389/fonc.2021.786191 |
| الإتاحة: | https://doi.org/10.3389/fonc.2021.786191Test https://doaj.org/article/8ac7559f52274598852b4ce0df5c1d1fTest |
| رقم الانضمام: | edsbas.6904C2FC |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2234943X |
|---|---|
| DOI: | 10.3389/fonc.2021.786191 |