Gadolinium-diethylenetriamine pentaacetic acid-carboxymethylarabinogalactan

[Gd-DTPA-CMAG-A₂]

Background

[PubMed]

Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. 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; 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 (1). Cross-linked iron oxide (CLIO) nanoparticles and other iron oxide formulations affect T2 primarily and lead to decreased signals. On the other hand, paramagnetic T1 agents such as gadolinium (Gd³⁺) and manganese (Mn²⁺) accelerate T1 relaxation and lead to increased contrast images.

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 (2, 3). Gd-labeled diethylenetriaminepentaacetic 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 in cancer tissues. Furthermore, they are largely nonspecific. Arabinogalactan, a polysaccharide, binds specifically to hepatocytes via asialoglycoprotein receptor (ASGP-R) (4-6). Li et al. (7) prepared aminated carboxymethylarabinogalactan (CMAG-A₂) to link with Gd-DTPA to form Gd-DTPA-CMAG-A₂ for imaging the liver via ASGP-R.

Synthesis

[PubMed]

DTPA-CMAG-A₂ was prepared by incubation of DTPA succinimide ester (~14 mmol) and CMAG-A₂ (0.51 mmol) (pH 10) at room temperature for 24 h (7). GdCl₃•6 H₂O was added to the solution of DTPA-CMAG-A₂ (1.2:1 molar ratio) and incubated at room temperature for 18–20 h. The product, Gd-DTPA-CMAG-A₂, was isolated with column chromatography. DTPA-CMAG-A₂ had 0.51 mmol of DTPA/g.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Gd-DTPA-CMAG-A₂ and Gd-DTPA exhibited T1 relaxivity r₁ values (0.47 T) of 7.9 and 5.4 mM^-1s^-1 at 37°C in buffer containing bovine serum albumin, respectively (7). The r₁ value of Gd-DTPA-CMAG-A₂ was not affected by the addition of equal molar of Ca²⁺ or ethylenediaminetetraacetic acid.

Animal Studies

Human Studies

[PubMed]

No publication is currently available.