Gold nanoparticles coated with dithiolated diethylenetriamine pentaacetic acid-gadolinium chelate

The gold nanoparticles (AuNPs) coated with dithiolated diethylenetriamine pentaacetic acid (DTDTPA)-gadolinium (Gd(III)) chelate, abbreviated as Au@DTDTPA-Gd (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 cm/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 cm/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-Gd) 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-Gd in MRI/CT imaging (1).