Biotinylated bovine serum albumin linked to gadolinium diethylenetriaminepentaacetic acid

An interaction between the epithelium and the surrounding stromal tissue that are separated by a basement membrane is responsible for maintenance of the epithelial tissue. Also, the stroma contains fibroblasts, leukocytes, and epithelial cells that are embedded in an extracellular matrix. Development of an epithelial carcinoma caused by a transformation of the epithelium results in stromal changes that involve the fibroblastic stroma and are considered essential for progression of the solid cancerous tumors (1-3). The fibroblasts in the stroma are believed to differentiate into myofibroblasts that have contractile properties and characteristically produce α-smooth muscle actin (α-SMA). The myofibroblasts have been shown to participate in tumor angiogenesis that is considered essential for maintenance and progression of the Cancer (1, 4-6). The myofibroblasts in turn differentiate into pericyte-like cells, and there is evidence suggesting that these cells play an important function in angiogenesis (7). Because several cell types are involved in the angiogenic process, the exact interaction between the various cell types, particularly the endothelial cells, the fibroblasts, and the myofibroblasts, is unclear. Granot et al. suggested that in vivo monitoring of the different cell types may reveal the function of each cell type in the tumor angiogenesis process (8).

The technique of magnetic resonance imaging (MRI) with the use of ferromagnetic or fluorinated nanoparticles has been used successfully to investigate cell dynamics in an in vivo setting (9, 10). Granot et al. used a similar approach to study the migration of fibroblasts after labeling them with biotinylated bovine serum albumin linked to gadolinium diethylenetriamine pentaacetate (biotin-BSA-GdDTPA) (8). Biotin-BSA-GdDTPA was also labeled with 5(6)-carboxyfluorescein succinimidyl ester (biotin-BSA-GdDTPA-FAM) to study uptake of the contrast agent (CA) by the myofibroblasts (8). Biotinylated BSA was used to facilitate labeling with avidin-conjugated 5(6)fluorescein isothiocyanate-mixed isomer (FITC) to study the biodistribution of biotin-BSA-GdDTPA in nude mice bearing fibroblast cell xenograft tumors in the hind limbs.