Imaging of tumour neovasculature by targeting the TGF-beta binding receptor endoglin.
In vivo imaging of endothelial markers in intact tumour neovasculature would have applications in assessing the efficacy of anti-angiogenic agents in clinical trials. Although a variety of different endothelial markers have been described, few have been evaluated as imaging markers. The transforming growth factor-beta (TGF-beta) binding receptor endoglin is a proliferation-associated endothelial marker. We hypothesised that endoglin would be an ideal target for imaging since it is strongly upregulated in proliferating endothelial cells of the tumour neovasculature. We used a radiolabelled monoclonal anti-endoglin antibody and compared its neovascular binding, accumulation and in vivo behaviour to an isotype-matched control IgG(2a). Our data show that the probe binds specifically and rapidly within minutes in vivo and that correlative autoradiography and immunohistology support the in vivo imaging findings. Imaging of abundantly expressed endothelial targets circumvents delivery barriers normally associated with other tumour targeting strategies, and can potentially be used to quantitate molecular angiogenic markers.
Bredow
S
S
Center for Molecular Imaging Research, Massachusetts General Hospital/Harvard Medical School, Department of Radiology, 149, 13th Street, 5416, Charlestown, MA 02129, USA. bredow@helix.mgh.harvard.edu
Lewin
M
M
Hofmann
B
B
Marecos
E
E
Weissleder
R
R
D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071063:Endoglin; D006801:Humans; D007150:Immunohistochemistry; D008546:Melanoma, Experimental / Q000098:blood supply / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1