| Autor: |
Terry, S.Y., Boerman, Otto C., Gerrits, Danny, Franssen, G.M., Metselaar, Josbert Maarten, Lehmann, S., Oyen, Wim J.G., Gerdes, C.A., Abiraj, K. |
| Přispěvatelé: |
Biomaterials Science and Technology, Faculty of Science and Technology |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
European journal of nuclear medicine and molecular imaging, 42(9), 1430-1438. Springer |
| ISSN: |
1619-7070 |
| Popis: |
Purpose Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. Methods The immunoreactive fraction and IC50 of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with 111In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with 111In-anti-F4/80-A3-1 and isotype-matched control antibody 111In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. Results In vitro binding assays showed that 111In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 % and IC50 was 0.58 nM. In vivo, injection of 10 or 100 μg 111In-anti-F4/80-A3-1 resulted in splenic uptake of 78 %ID/g and 31 %ID/g, respectively, and tumour uptake of 1.38 %ID/g and 4.08 %ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg 111In-anti-F4/80-A3-1 from 248 %ID/g to 114 %ID/g and reduced 111In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of 111In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of 111In-rat IgG2b was lower in the spleen, liver and femur when compared to 111In-anti-F4/80-A3-1. Conclusion Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen sink organs for macrophage-specific tracers. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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