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Gold nanoparticles coated with dithiolated diethylenetriamine pentaacetic acid-gadolinium chelate

, PhD
National Center for Biotechnology Information, NLM, NIH

Created: ; Last Update: November 17, 2010.

Chemical name:Gold nanoparticles coated with dithiolated diethylenetriamine pentaacetic acid-gadolinium chelate
Abbreviated name:Au@DTDTPA-Gd50
Agent Category:Nanoparticles
Target Category:Non-targeted
Method of detection:Multimodality imaging (magnetic resonance imaging/computed tomography (MRI/CT))
Source of signal / contrast:Au and Gd(III)
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The gold nanoparticles (AuNPs) coated with dithiolated diethylenetriamine pentaacetic acid (DTDTPA)-gadolinium (Gd(III)) chelate, abbreviated as Au@DTDTPA-Gd50 (Au = 10 mg/ml; Gd(III) = 5 mM), are a magnetic resonance imaging (MRI)/computed tomography (CT) dual-imaging agent synthesized by Alric et al. for MRI/CT bimodal imaging (1).

Development of hybrid imaging technology has triggered great effort in probe development to boost the benefits of hybrid instrument technology (2-4). In contrast to other agents, multimodal imaging agents for MRI/CT have rarely been explored, although MRI and CT are frequently applied to the same patients for precise diagnosis and treatment evaluation (5-7). Recently, AuNPs have been shown to induce strong contrast enhancement as X-ray contrast agents (1, 8). These particles exhibit a higher X-ray absorption coefficient than iodinated compounds (5.16 and 1.94 cm2/g, respectively, at 100 keV). Furthermore, AuNPs are easily controlled with regard to size, shape, and surface modification (9). Gd(III) also possesses a higher X-ray absorption coefficient (3.11 cm2/g at 100 keV) than iodine, although this value is lower than that of gold. Interestingly, when Gd(III) ions are bound to NPs, they exhibit a much higher relaxivity than that of clinically approved Gd(III)-chelates (8, 9). Sanchez et al. have shown that the water-soluble apoferritin-encapsulated gadolinium oxide-hydroxide NPs (Gd-Apoferritin) exhibit 10 and 70 times higher T1 and T2 relaxivity values, respectively, than those of classic Gd(III)-complexes (Omniscan® and Gd-DTPA) (8).

On the basis of these facts, Gd(III)-coated AuNPs have been hypothesized to be an efficient dual agent for MRI/CT imaging. Alric et al. demonstrated that Gd(III) chelate-coated AuNPs (Au@DTDTPA-Gd50) provide strong X-ray absorption and R1 relaxivity (1). The contrast enhancement in MRI stems from the presence of Gd(III) ions that are entrapped in the organic shell, whereas the gold core provides strong X-ray absorption. These particles are small enough (2–2.5 nm) to circulate freely in the blood vessels without undesirable accumulation in organs such as lungs, spleen, and liver. Park et al. developed a MRI/CT dual-imaging agent with Gd(III) and gold reporters (Au@GdL) (9). Au@GdL NPs are generated by encapsulating gold cores within a multilayered organic shell, and they have been shown to accumulate in tumor xenografts in animals (9). This chapter summarizes the data obtained with Au@DTDTPA-Gd50 in MRI/CT imaging (1).



Au@DTDTPA-Gd NPs were synthesized by reducing gold salt (HAuCl4 ·3H2O) with sodium borohydride (NaBH4) in the presence of dithiolated derivatives of diethylenetriamine pentaacetic acid (1). With a molar ratio of 0.104 for gold to NaBH4 and 1.020 for gold to DTDTPA, the Au@DTDTPA-Gd NPs were composed of an AuNP core (2.4 nm in diameter) and an organic shell with ~150 DTDTPA and ~150 Gd(III) per particle (Au@DTDTPA150). However, the incorporation of 150 Gd(III) per particle altered the colloidal stability for gold content to a great extent (>1 mg/ml). This lack of stability was overcome by reducing Gd(III) to ~50 per particle (Gd to DTDTPA molar ratio: 0.33) (Au@DTDTPA-Gd50). The zeta potential of Au@DTDTPA-Gd50 was −25 mV at pH 7.4 with 0.01 M NaCl, which is weaker than that of Au@DTDTPA (−32 mV), but the negative charge was sufficiently strong to ensure the colloidal stability (gold content: 10 mg/ml) in the physiological medium (pH 7.4, 150 mM NaCl) for at least 1 week.

Synchrotron radiation computed tomography (SRCT) of the phantoms containing Au@DTDTPA at various gold concentrations (0.14–10 mg/ml; 0.71 ≤ Au ≤ 50.7 mM) and Au@DTDTPA-Gd50 (5.6 mg/ml; Au = 28.4 mM) showed that these particles induced a contrast enhancement when the gold concentration was at least equal to 1.4 mg/ml. Conventional CT analysis revealed that 50.7 mM Au@DTDTPA (10 mg Au/ml) exhibited an equivalent X-ray absorption of 280 mM iodine (35 mg iodine/ml). The R1 relaxivity of the Au@DTDTPA-Gd50 was similar to that of Au@DTDTPA150 (3.9 mM-1s-1) (1). Au@DTDTPA-Gd50 (10 mg Au/ml and 5 mM Gd(III) in 150 mM NaCI hepes-buffered solution at pH 7.4) was used for in vivo studies.

In Vitro Studies: Testing in Cells and Tissues


No references are currently available.

Animal Studies



SRCT and MRI were performed before and after intravenous injection of 300 µl Au@DTDTPA-Gd50 colloid in mice and 0.6–1.8 ml Au@DTDTPA-Gd50 colloid in rats (1).

For SRCT, kidneys could be detected at 3 min after injection, and the ureter and urinary tract could be delineated at 10 min after injection. The gold concentrations in the kidneys, ureter, and bladder at 10 min were 2.59, 5.50, and 5.77 mg/ml, respectively. The number of gold NPs in the kidneys was almost constant between 10 min and 30 min and became too low to determine at 45 min. Presence of gold in the urine and kidneys was confirmed with inductively coupled plasma-mass spectrometry of the organs of a rat euthanized at 25 min after injection. The uptake in the lung, liver, spleen, and heart was lower than that in the kidneys and could be attributed to the presence of blood in these organs because the gold content was almost the same as that in the heart.

MRI in the rats and mice yielded results identical to those obtained with SRCT. Although the Gd(III) content in the Au@DTDTPA-Gd50 was lower than the gold content (5 mM versus 50.7 mM), the contrast induced by these particles was higher with MRI than with SRCT. At 45 min after injection, the contrast in the kidneys was still obvious.

Other Non-Primate Mammals


No references are currently available.

Non-Human Primates


No references are currently available.

Human Studies


No references are currently available.


Alric C., Taleb J., Le Duc G., Mandon C., Billotey C., Le Meur-Herland A., Brochard T., Vocanson F., Janier M., Perriat P., Roux S., Tillement O. Gadolinium chelate coated gold nanoparticles as contrast agents for both X-ray computed tomography and magnetic resonance imaging. J Am Chem Soc. 2008;130(18):5908–15. [PubMed: 18407638]
Boss A., Bisdas S., Kolb A., Hofmann M., Ernemann U., Claussen C.D., Pfannenberg C., Pichler B.J., Reimold M., Stegger L. Hybrid PET/MRI of intracranial masses: initial experiences and comparison to PET/CT. J Nucl Med. 2010;51(8):1198–205. [PubMed: 20660388]
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Cherry S.R. Multimodality imaging: beyond PET/CT and SPECT/CT. Semin Nucl Med. 2009;39(5):348–53. [PMC free article: PMC2735449] [PubMed: 19646559]
Jennings L.E., Long N.J. 'Two is better than one'--probes for dual-modality molecular imaging. Chem Commun (Camb) 2009;(24):3511–24. [PubMed: 19521594]
Lee S., Chen X. Dual-modality probes for in vivo molecular imaging. Mol Imaging. 2009;8(2):87–100. [PubMed: 19397854]
Louie A. Multimodality imaging probes: design and challenges. Chem Rev. 2010;110(5):3146–95. [PMC free article: PMC2878382] [PubMed: 20225900]
Sanchez P., Valero E., Galvez N., Dominguez-Vera J.M., Marinone M., Poletti G., Corti M., Lascialfari A. MRI relaxation properties of water-soluble apoferritin-encapsulated gadolinium oxide-hydroxide nanoparticles. Dalton Trans. 2009;(5):800–4. [PubMed: 19156273]
Park J.A., Kim H.K., Kim J.H., Jeong S.W., Jung J.C., Lee G.H., Lee J., Chang Y., Kim T.J. Gold nanoparticles functionalized by gadolinium-DTPA conjugate of cysteine as a multimodal bioimaging agent. Bioorg Med Chem Lett. 2010;20(7):2287–91. [PubMed: 20188545]
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