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Four gadolinium (Gd)-based macromolecular contrast agents, G3-(Gd-DOTA) 24, G5-(Gd-DOTA) 96, G3-(Gd-DTPA) 24, and G5-(Gd-DTPA) 96, were prepared that varied in the size of dendrimer (generation three and five), the type of chelate group (DTPA or DOTA), and the theoretical number of metallated chelates (24 and 96). Synthesis relied on a dichlorotriazine derivatized with a DOTA or DTPA ligand that was incorporated into the dendrimer and ultimately metallated with Gd ions. Paramagnetic characteristics and in vivo pharmacokinetics of all four contrast agents were investigated. The DOTA-containing agents, G3-(Gd-DOTA) 24 and G5-(Gd-DOTA) 96, demonstrated exceptionally high r1 relaxivity values at off peak magnetic fields. Additionally, G5-(Gd-DOTA) 96 showed increased r1 relaxivity in serum compared to that in PBS, which was consistent with in vivo images. Download Lagu Bruno Mars Today My Life Begins Free more.

While G3-(Gd-DOTA) 24 and G3-(Gd-DTPA) 24 were rapidly excreted into the urine, G5-(Gd-DOTA) 96 and G5-(Gd-DTPA) 96 did not clear as quickly through the kidneys. Molecular simulation of the DOTA-containing dendrimers provides a single-molecular level characterization of the structures and suggests that a majority of the metallated ligands are accessible to water. These triazine dendrimer-based MRI contrast agents exhibit several promising features such as high in vivo r1 relaxivity, desirable pharmacokinetics, and well-defined structure. INTRODUCTION Numerous nanomaterials—inorganic, organic, and hybrid—with unique chemical and physical characteristics are being explored for biologic application. Hangaroo Download Full Version more. Among them, synthetic dendritic macromolecules are versatile and promising for biological and medical applications because of their flexible, reproducible syntheses and biocompatible characteristics. Synthesis The macromolecular Gd 3+ chelates were synthesized using the triazine dendrimers of generation 3 and 5 prepared as previously reported. To incorporate either DOTA or DTPA groups, a conjugation strategy using a functionalized monomer was adopted ().

That is, the t-butyl ester-protected ligands were incorporated into the dichlorotriazine 5 or 8 in 88% yield. Reactions with the dendrimer platforms afforded the four poly(monochlorotriazine) dendrimers, 6, 7, 9, and 10, respectively. The surface group HEEP, 1-[2-(2-hydroxyethoxy)ethyl]piperazine, was chosen due to high reactivity of the cyclic secondary amine towards monochlorotriazines and the hydrophilic auxiliary groups. Following an acidic deprotection, the desired macromolecular ligands, 1, 2, 3, and 4 were obtained. From the G3 and G5 dendritic platforms, these agents were synthesized in four steps in 70-80% overall yield. Preparation of Gd(III) Complexes The dendrimers ( 1-4) were dissolved in deionized water. Gd(OAc) 3 (24 equiv.