Chunchao Xia, Presenter: Nothing to Disclose

Hua Ai PhD, Abstract Co-Author: Nothing to Disclose

Bin Song MD, Abstract Co-Author: Nothing to Disclose

Qiyong Gong, Abstract Co-Author: Nothing to Disclose

Changqiang Wu, Abstract Co-Author: Nothing to Disclose

Bingbing Lin, Abstract Co-Author: Nothing to Disclose

Danyang Li, Abstract Co-Author: Nothing to Disclose

Magnetic resonance imaging (MRI) has shown its advantages in early diagnosis, drug discovery, medical implant evaluation and other important noninvasive imaging monitoring processes.1, 2 However, the sensitivity of free gadolinium complexes, such as Gd-DOTA, are poor for cellular and molecular imaging. One facile option to increase the sencitivity is conjugation of Gd(III) complexes on rigid macromolecules or nanoparticles.3 In this study, polymeric micelles of amphiphilic starlike dextran was used as nanoplatforms for conjugation of Gd-DOTA to form polymer nanoparticles with multivalent Gd-DOTA on their surface (Scheme 1). The T1 relaxivity was characterized under a clinical 1.5T MRI scanner and showing much higher sensitivity than free Gd-DOTA complexes.

Methods: Amphiphilic starlike dextran β-CD-Dex-g-SA/alkyne was synthesized following a “coupling onto” approach via the click chemistry reaction between heptakis-6-azido-6-deoxy-β-cyclodextrin and alkyne dextran according to the previous reference.4 Multiple Gd-DOTA-N3 molecules were then grafted onto the surface of micelles of β-CD-Dex-g-SA/alkyne in water. T1 relaxivities of the multivalent micelles and Gd-DOTA complexes were measured at 1.5 T under a clinical MRI scanner (Siemens Sonata). Macrophages and other cell lines labeled with this multivalent probes were imaged under a 3T clinical MRI scanner.  

Amphiphilic starlike dextran β-CD-Dex-g-SA/alkyne was synthesized and characterized by 1H NMR. SEM and DLS data shows that it can assemble into micelles with a diameter of ~100 nm. T1 relaxivity of the resulted multivalent Gd-DOTA nanoparticles and free Gd-DOTA in water was shown in Figure 1, β-CD-Dex-g-SA/Gd-DOTA nanoparticles has a much higher T1 relaxivity of 18.1 Gd mM−1s−1 than that of Gd-DOTA (4.0 Gd mM−1s−1). Cells labeled with this multivalent probes have shown strong contrast against unlabeled cells under a 3T clinical MRI scanner (Figure 2).

β-CD-Dex-g-SA/Gd-DOTA nanoparticles as a sensitive MRI probe via rigid triazole ring of click chemistry were successfully prepared. T1 relaxivity of the probe was increased by almost 350% compared to that of free Gd-DOTA. Cells labeled with the probe also have shown strong contrast against unlabeled cells.

Gd-DOTA decorated amphiphilic dextran nanoparticles with much higher sensitivity than free Gd-DOTA are potential MRI probes used for cellular and molecular imaging.

Xia, C, Ai, H, Song, B, Gong, Q, Wu, C, Lin, B, Li, D, Gd-DOTA Decorated Amphiphilic Dextran Nanoparticles as Sensitive MRI Probes.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14010371.html