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cNGR: A novel homin...
cNGR: A novel homing sequence for CD13/APN targeted molecular imaging of murine cardiac angiogenesis in vivo
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- Buehler, Alexandra (författare)
- CARIM, University of Maastricht, The Netherlands
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- van Zandvoort, Marc (författare)
- CARIM, University of Maastricht, The Netherlands
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- Stelt, Bram (författare)
- CARIM, University of Maastricht, The Netherlands
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- Hackeng, Tilman (författare)
- CARIM, University of Maastricht, The Netherlands
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- Schrans-Stassen, Bianca (författare)
- CARIM, University of Maastricht, The Netherlands
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- Bennaghmouch, Abdelkader (författare)
- CARIM, University of Maastricht, The Netherlands
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- Hofstra, Leo (författare)
- CARIM, University of Maastricht, The Netherlands
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- Cleutjens, Jack (författare)
- CARIM, University of Maastricht, The Netherlands
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- Duijvestijn, Adriaan (författare)
- CARIM, University of Maastricht, The Netherlands
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- Smeets, Mirjam (författare)
- University Hospital Utrecht, The Netherlands
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- de Kleijn, Dominique (författare)
- University Hospital Utrecht, The Netherlands
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- Post, Mark (författare)
- University Hospital Utrecht, The Netherlands
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- de Muinck, Ebo D. (författare)
- Dartmouth Medical School, Hanover, NH, USA
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(creator_code:org_t)
- American Heart Association, 2006
- 2006
- Engelska.
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : American Heart Association. - 1079-5642 .- 1524-4636. ; 26:12, s. 2681-2687
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- OBJECTIVE:Previously, the peptide sequence cNGR has been shown to home specifically to CD13/APN (aminopeptidase N) on tumor endothelium. Here, we investigated the feasibility of selective imaging of cardiac angiogenesis using the cNGR-CD13/APN system.METHODS AND RESULTS:CD13/APN induction and cNGR homing were studied in the murine myocardial infarction (MI) model. By real-time polymerase chain reaction (PCR) at 7 days after MI, CD13/APN expression was 10- to 20-fold higher in the angiogenic infarct border zone and the MI area than in non-MI areas. In vivo fluorescence microscopy confirmed specific homing of fluorophore-tagged cNGR to the border zone and MI territory at 4 and 7 days after MI with a local advantage of 2.3, but not at 1 or 14 days after MI. Tissue residence half-life was 9.1+/-0.3 hours, whereas the half-life in plasma was 15.4+/-3.4 minutes. Pulse chase experiments confirmed reversible binding of cNGR in the infarct area. Fluorescent labeled cNGR conjugates or antibodies were injected in vivo, and their distribution was studied ex vivo by 2-photon laser scanning microscopy (TPLSM). cNGR co-localized exclusively with CD13/APN and the endothelial marker CD31 on vessels.CONCLUSIONS:In cardiac angiogenesis endothelial CD13/APN is upregulated. It can be targeted specifically with cNGR conjugates. In the heart cNGR binds its endothelial target only in angiogenic areas.
Nyckelord
- aminopeptidase N; angiogenesis; molecular imaging; NGR; vascular biology
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Buehler, Alexand ...
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van Zandvoort, M ...
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Stelt, Bram
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Hackeng, Tilman
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Schrans-Stassen, ...
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Bennaghmouch, Ab ...
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visa fler...
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Hofstra, Leo
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Cleutjens, Jack
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Duijvestijn, Adr ...
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Smeets, Mirjam
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de Kleijn, Domin ...
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Post, Mark
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de Muinck, Ebo D ...
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