Angiogenesis is an essential process in the development of new blood vessels both in normal physiological states and diseases (1, 2). Targeting of tumor vasculature is a promising strategy for tumor imaging and therapy because tumor growth and metastasis largely depend on angiogenesis (3-5). Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that modulates blood vessel development, angiogenesis, and tumor progression (6). There are three isoforms of TGF-β (β1, β2, and β3). TGF-β1 inhibits proliferation and migration of endothelial cells and their ability to form capillaries. CD105 (endoglin, EDG) is a homodimeric transmembrane glycoprotein (180 kDa) with disulfide-linked subunits of 95 kDa. CD105 is a component of the TGF-β receptor complex that specifically binds TGF-β1 and TGF-β3 with high affinity (7). CD105 is important for blood vessel development. The expression of CD105 on different cells affects cellular response to TGF-β1. CD105 is overexpressed in proliferating endothelial cells of tumor vessels, and CD105 prevents TGF-β1-mediated inhibition of endothelial cell proliferation (8, 9).
Radiolabeled monoclonal antibodies (mAbs) have been developed for both the diagnosis and treatment of tumors (10-12). Quiescent human endothelial cells express CD105 only weakly, but the expression of CD105 is strongly upregulated on the endothelial cells of tumor tissues undergoing angiogenesis (9, 13). Anti-CD105 mAbs, such as MAEND3, E9, and MJ7/18 with radioisotopes (e.g., 111In, 99mTc, and 125I) have been studied as single-photon emission computed tomography (SPECT) probes for imaging CD105 expression (9, 14). TRC105 is a human/murine chimeric IgG1 mAb that binds with higher affinity to human CD105 than to murine CD105 (15). TRC105 inhibits angiogenesis and tumor growth and is now in clinical trials in cancer patients. Hong et al. (16) showed that 64Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-anti-CD105 TRC105 (64Cu-DOTA-TRC105) mAbs could efficiently image 4T1 murine breast tumor in mice with positron emission tomography (PET) imaging. Hong et al. (17) also evaluated 89Zr-desferrioxamine-TRC105 (89Zr-Df-TRC105) as a 89Zr-based PET agent in the same 4T1 murine breast tumor model.