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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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Gadolinium-diethylenetriamine pentaacetic acid-carboxymethylarabinogalactan

Gd-DTPA-CMAG-A2
, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD, vog.hin.mln.ibcn@dacim

Created: ; Last Update: January 6, 2009.

Chemical name:Gadolinium-diethylenetriamine pentaacetic acid- carboxymethylarabinogalactan
Abbreviated name:Gd-DTPA-CMAG-A2
Synonym:
Agent category:Polysaccharide
Target:Hepatic asialoglycoprotein receptor (ASGP-R)
Target category:Receptor
Method of detection:Magnetic resonance imaging (MRI)
Source of signal/contrast:Gadolinium, Gd
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
No structure is available in PubChem.

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

Rodents

[PubMed]

Li et al. (7) performed dynamic T1-weighted MRI imaging (4.7 T) studies in rats (n = 3) after injection of Gd-DTPA-CMAG-A2 (79 nmol/kg) or Gd-DTPA (96 nmol/kg). The mean enhancement of the liver parenchyma and kidney was 38.7 ± 6.4% and 69.4 ± 4.4% for Gd-DTPA-CMAG-A2 at 10–30 min, respectively. On the other hand, the mean enhancement of the liver parenchyma and kidney was 21.9 ± 4.5% and 53.8 ± 4.8% for Gd-DTPA at 10–30 min, respectively. The hepatic uptake rate of Gd-DTPA-CMAG-A2 (half-life (t1/2), 0.8 min) was faster than that of Gd-DTPA (t1/2, 16.7 min), whereas the liver excretion rate of Gd-DTPA-CMAG-A2 (t1/2, 129.8 min) was slower than that of Gd-DTPA (t1/2, 52.4 min). The renal uptake rate of Gd-DTPA-CMAG-A2 (t1/2, 0.1 min) was faster than that of Gd-DTPA (t1/2, 4.6 min), whereas the renal excretion rate of Gd-DTPA-CMAG-A2 (t1/2,153.8 min) was slower than that of Gd-DTPA (t1/2, 86.1 min). Rats receiving Gd-DTPA-CMAG-A2 exhibited increases in the MR signal intensity in the liver comparing with Gd-DTPA at 10-90 min after injection. No blocking experiment was performed.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

References

1.
Wang Y.X., Hussain S.M., Krestin G.P. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol. 2001;11(11):2319–31. [PubMed: 11702180]
2.
Brasch R.C. New directions in the development of MR imaging contrast media. Radiology. 1992;183(1):1–11. [PubMed: 1549653]
3.
Runge V.M., Gelblum D.Y. Future directions in magnetic resonance contrast media. Top Magn Reson Imaging. 1991;3(2):85–97. [PubMed: 2025435]
4.
Gallez B., Lacour V., Demeure R., Debuyst R., Dejehet F., De Keyser J.L., Dumont P. Spin labelled arabinogalactan as MRI contrast agent. Magn Reson Imaging. 1994;12(1):61–9. [PubMed: 8295509]
5.
Groman E.V., Enriquez P.M., Jung C., Josephson L. Arabinogalactan for hepatic drug delivery. Bioconjug Chem. 1994;5(6):547–56. [PubMed: 7533005]
6.
Prata M.I., Santos A.C., Torres S., Andre J.P., Martins J.A., Neves M., Garcia-Martin M.L., Rodrigues T.B., Lopez-Larrubia P., Cerdan S., Geraldes C.F. Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic asyaloglycoprotein receptor: cell internalization and animal imaging studies. Contrast Media Mol Imaging. 2006;1(6):246–58. [PubMed: 17191765]
7.
Li W., Li Z., Jing F., Deng Y., Wei L., Liao P., Yang X., Li X., Pei F., Wang X., Lei H. Synthesis and evaluation of Gd-DTPA-labeled arabinogalactans as potential MRI contrast agents. Carbohydr Res. 2008;343(4):685–94. [PubMed: 18258223]
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