Abstract

Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs), which showed longitudinal relaxivity (r1) values about four times higher than that of clinically used Gd-DTPA (Magnevist®, Bayer). In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T). In this study, the association constants (Ka) of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA), measured and calculated with a quartz crystal microbalance (QCM) in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The Ka values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.

Highlights

  • Magnetic resonance imaging (MRI) is one of the most important non-invasive imaging modalities for disease diagnosis, and there has been dramatic progress in this field over the past 30 years [1,2,3]

  • We found that the pharmacokinetic difference derived from both the chirality and the generation of chiral dendrimer Gd-MRI CAs can be evaluated by in vivo MRI and estimated by in vitro quartz crystal microbalance (QCM)

  • While the exact amount of the substrate that adhered to the quartz surface can be calculated using the Sauebrey equation [34], the association constant (Ka ) of our synthesized chiral dendrimer Gd-MRI CAs with bovine serum albumin (BSA), which is a model of plasma protein, was estimated by a change in mass on the quartz surface covered with BSA, after the sequential addition of synthesized CAs

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Summary

Introduction

Magnetic resonance imaging (MRI) is one of the most important non-invasive imaging modalities for disease diagnosis, and there has been dramatic progress in this field over the past 30 years [1,2,3]. We found that the pharmacokinetic difference derived from both the chirality and the generation of chiral dendrimer Gd-MRI CAs can be evaluated by in vivo MRI and estimated by in vitro QCM. These results are consistent with each other. While the exact amount of the substrate that adhered to the quartz surface can be calculated using the Sauebrey equation [34], the association constant (Ka ) of our synthesized chiral dendrimer Gd-MRI CAs with bovine serum albumin (BSA), which is a model of plasma protein, was estimated by a change in mass on the quartz surface covered with BSA, after the sequential addition of synthesized CAs

General Methods
Synthesis
Relaxation Time Measurements
Cytotoxicity Assay
Discussion mice atand
Synthesis of 2nd- and 3rd-Generation
Evaluation
Cytotoxicity of Chiral Dendrimer Gd-MRI CAs
Evaluation and Pharmacokineticsofof
Frequency
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