Improving Proton Relaxivity of Dendritic MRI Contrast Agents by Rigid Silsesquioxane Core

Abstract

We report that the cubic octameric polyhedral oligomeric silsesquioxanes (POSS)-core dendrimers, novel gadolinium (Gd) chelators, enhanced the proton relaxivity to Gd 3þ . The stability of the Gd complex with POSS(G1.5) was similar to those of DOTA and DTPA. From the MTT assay with the primary hepatocytes, the cytotoxicity of [Gd 2 POSS(G1.5)]2À showed lower than that of the [Gd(DOTA)]À complex. The detection limits were approximately 100-fold improved than those of DOTA and DTPA-Gd complexes in the MR images.KEY WORDS: MRI / Contrast Agent / Silsesquioxane / Dendrimer / Gadolinium / POSS / Magnetic resonance imaging (MRI) is one of powerful diagnostic tools in modern clinical medicine, and paramagnetic complexes, which have the ability to enhance the proton relaxation rate of water tissue, are used as contrast agents for improving sensitivity and specificity. The most commonly used positive contrast agents nowadays are thermodynamically and kinetically stable low molecular weight gadolinium compounds based on a polyaminocarboxylate motif (linear DTPA and cyclic DOTA respectively) for suppressing the toxicity of Gd 3þ and accelerating the proton relaxation rate of water tissue coordinated to Gd 3þ . 1 Since contrast agents with high relaxivity can be detected at lower doses, the relaxation mechanism and a number of predominant parameters to achieve sufficient T 1 change have been studied.

Thermodynamic study of POSS-based ionic liquids with various numbers of ion pairs

“…The decomposition temperatures (T d ) were determined from the onset of the weight loss. 29 Si NMR spectra assigned to the T 8 POSS structure.…”

“…Moreover, the molecular motion of substituents of the POSS core can be efficiently restricted because of the rigidity of the silica framework. 29 Indeed, POSS has been used as a filler for improving the thermal and mechanical properties of conventional plastics by suppressing the molecular rotation of polymer chains. 30 Herein, we prepared a series of modified POSS with variable numbers of imidazolium-carboxylate pairs (n¼2, 4, 6 and 8) and investigated the relationships between structures and thermal properties ( Figure 1).…”

Chemicals-Inspired Biomaterials: Developing Biomaterials Inspired by Material Science Based on POSS

“…To enhance the sensitivity and suppress the toxicity of the Gd-based contrast agent, various chelators were synthesized. 22 It is known that the suppression of the molecular motion of Gd ions in a complex can induce increase of the relaxivity in clinically-used magnetic fields. 22 Hence, polymer or macromolecule-based contrast agents have been developed for enhancing the relaxivity.…”

“…22 It is known that the suppression of the molecular motion of Gd ions in a complex can induce increase of the relaxivity in clinically-used magnetic fields. 22 Hence, polymer or macromolecule-based contrast agents have been developed for enhancing the relaxivity. We aimed to provide a new strategy for molecular design of highly-sensitive contrast agents by presenting new parameters other than the increase of molecular weight.…”

“…To investigate the validity of this hypothesis, we designed and synthesized a series of chelators for Gd ions based on POSScore dendrimers (Figure 2). 22 The Gd complexes with various sizes of POSS-core dendrimers were prepared, and from the MR image of the solutions, the sensitivity was investigated. From the T 1 -weighted images, the sensitivity was evaluated from the detection limits and compared to those of the conventional products, DOTA and DTPA complexes.…”