Gadolinium-diethylenetriamine tetraacetic acid-icosahedral -borane scaffold

Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally (1). Protons (hydrogen nuclei) are widely used in imaging because of their abundance in water molecules. Water comprises 80% of most soft tissue. The contrast of proton MRI depends primarily on the density of the nucleus (proton spins), the relaxation times of the nuclear magnetization (T1, longitudinal, and T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. However, insufficient contrast between normal and diseased tissues requires the development of contrast agents. Most contrast agents affect the T1 and T2 relaxation times of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field. Cross-linked iron oxide nanoparticles and other iron oxide formulations affect T2 primarily and lead to decreased signals. On the other hand, paramagnetic T1 agents, such as gadolinium (Gd) and manganese (Mn), accelerate T1 relaxation and lead to brighter contrast images (2). Gadolinium (Gd), a lanthanide metal ion with seven unpaired electrons, has been shown to be very effective in enhancing proton relaxation because of its high magnetic moment and water coordination (3, 4). Gd-Labeled diethylenetriamine pentaacetic acid (Gd-DTPA) was the first intravenous MRI contrast agent used clinically, and a number of similar Gd chelates have been developed in an effort to further improve clinical use. However, these low molecular weight Gd chelates have short blood and tissue retention times, which limit their use as imaging agents in the vasculature and cancer. Furthermore, these low molecular weight MRI contrast agents exhibit low relaxivity value (4 mMs per Gd), high toxicity (nephrogenic systemic fibrosis in patients with renal dysfunction), and a lack of tissue specificity (5). Li et al. (6) have developed polyhedral boranes as a scaffold for the targeted high payload delivery of drugs and imaging agents. A functionalizable monodisperse molecular borane scaffold, [closoB(OH)], conjugated with twelve radial ethylene glycol (PEG) arms with attachments of Gd-labeled diethylenetriamine tetraacetic acid (Gd-DTTA) (CA-9). Goswami et al. (7) evaluated CA-9 for use as a high-performance MRI contrast agent in nude mice bearing human PC-3 prostate tumors.