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Clinical Cancer Research Vol. 6, 2037-2043, May 2000
© 2000 American Association for Cancer Research

Experimental Therapeutics, Preclinical Pharmacology

Endoglin Is a Suitable Target for Efficient Imaging of Solid Tumors: In Vivo Evidence in a Canine Mammary Carcinoma Model1

Ester Fonsatti2, Antti P. Jekunen2, Kalevi J. A. Kairemo, Sandra Coral, Marjatta Snellman, Maria Rita Nicotra, Pier Giorgio Natali, Maresa Altomonte and Michele Maio3

Advanced Immunotherapy Unit, Centro di Riferimento Oncologico, Istituto Nazionale di Ricovero e Cura a Carattere Scientifico, Aviano 33081, Italy [E. F., S. C., M. A., M. M.]; Departments of Clinical Pharmacology [A. P. J.], Nuclear Medicine [K. J. A. K.], and Clinical Veterinary Sciences [M. S.], Helsinki University, Helsinki 00014, Finland; and Institute of Biomedical Technologies, Consiglio Nazionale delle Ricerche [M. R. N.], and Laboratory of Immunology, Istituto Regina Elena [P. G. N.], Rome 00158, Italy

Increasing evidence suggests that endoglin (CD105) is a new powerful marker of neovascularization in solid malignancies; thus, using breast cancer as a model, we investigated whether targeting of CD105 by monoclonal antibody (mAb) MAEND3 can be used for in vivo imaging of solid tumors. Immunohistochemistry and flow cytometry identified differential expression of CD105 on breast cancer and endothelial cells; in fact, neoplastic cells were weakly and rarely stained by mAb MAEND3, which in contrast, strongly and invariably stained blood vessel endothelia within the breast adenocarcinomas investigated and cultured endothelial cells. Moreover, in contrast to CD31, which currently represents the reference marker to assess angiogenetic activity, CD105 expression was highest in semiconfluent and actively proliferating endothelial cells, and it progressively decreased as cells reached tight confluency and low [3H]thymidine uptake. i.v. administration of 18 MBq of 125I-labeled mAb MAEND3 efficiently imaged spontaneous mammary adenocarcinomas in two dogs; the uptake of radiolabeled mAb was rapid and intense because tumor:background ratios of 8.2:1 and 9.3:1 were reached 8 h after mAb administration, in the absence of immediate and/or long-term clinical side effects. Altogether, our present data suggest that targeting of CD105 on tumor-associated blood vessels may represent a new strategy for in vivo imaging of solid malignancies, regardless of their histological origin.




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