1. Nanobody-Based Targeting of the Macrophage Mannose Receptor for Effective In Vivo Imaging of Tumor-Associated Macrophages.
- Author
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Movahedi, Kiavash, Schoonooghe, Steve, Laoui, Damya, Houbracken, Isabelle, Waelput, Wim, Breckpot, Karine, Bouwens, Luc, Lahoutte, Tony, De Baetselier, Patrick, Raes, Geert, Devoogdt, Nick, and Van Ginderachter, Jo A.
- Subjects
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MACROPHAGES , *IMMUNOGLOBULINS , *CAMELIDAE , *LUNG cancer , *BREAST cancer , *LABORATORY mice - Abstract
Tumor-associated macrophages (TAM) are an important component of the tumor stroma and exert several tumor-promoting activities. Strongly pro-angiogenic TAMs that reside in hypoxic tumor areas highly express macrophage mannose receptor (MMR, CD206). In this study, we targeted MMR+ TAMs using nanobodies, which are single-domain antigen-binding fragments derived from Camelidae heavy-chain antibodies. MMR-specific nanobodies stained TAMs in lung and breast tumor single-cell suspensions in vitro, and intravenous injection of 99mTc-labeled anti-MMR nanobodies successfully targeted tumor in vivo. Retention of the nanobody was receptor-specific and absent in MMR-deficient mice. Importantly, co-injection of excess unlabeled, bivalent anti-MMR nanobodies reduced nanobody accumulation in extratumoral organs to background levels, without compromising tumor uptake. Within tumors, the 99mTc-labeled nanobodies specifically labeled MMR+ TAMs, as CCR2-deficient mice that contain fewer TAMs showed significantly reduced tumor uptake. Further, anti-MMR nanobodies accumulated in hypoxic regions, thus targeting pro-angiogenic MMR+ TAMs. Taken together, our findings provide preclinical proof of concept that anti-MMR nanobodies can be used to selectively target and image TAM subpopulations in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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