Endoglin is a suitable target for efficient imaging of solid tumors: In vivo evidence in a canine mammary carcinoma model

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. immunohistoch emistry and flow cytometry identified differential expression of CD105 on b reast cancer and endothelial cells; in fact, neoplastic cells were weakly a nd rarely stained by mAb MAEND3, which in contrast, strongly and invariably stained blood vessel endothelia within the breast adenocarcinomas investig ated and cultured endothelial cells. Moreover, in contrast to CD31, which c urrently represents the reference marker to assess angiogenetic activity, C D105 expression was highest in semi-confluent and actively proliferating en dothelial cells, and it progressively decreased as cells reached tight conf luency and low [H-3]thymidine uptake, i.v. administration of 18 MBq of I-12 5-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 admi nistration, in the absence of immediate and/or long-term clinical side effe cts. Altogether, our present data suggest that targeting of CD105 on tumor- associated blood vessels may represent a new strategy for in vivo imaging o f solid malignancies, regardless of their histological origin.