Gd(3+)-DTPA-Meglumine-Anionic Linear Globular Dendrimer G1: Novel Nanosized Low Toxic Tumor Molecular MR Imaging Agent.

Abstract

Despite the great efforts in the areas of early diagnosis and treatment of cancer, this disease continues to grow and is still a global killer. Cancer treatment efficiency is relatively high in the early stages of the disease. Therefore, early diagnosis is a key factor in cancer treatment. Among the various diagnostic methods, molecular imaging is one of the fastest and safest ones. Because of its unique characteristics, magnetic resonance imaging has a special position in most researches. To increase the contrast of MR images, many pharmaceuticals have been known and used so far. Gadopentetate (with commercial name Magnevist) is the first magnetic resonance imaging contrast media that has been approved by the US Food and Drug Administration. In this study, gadopentetate was first synthesized and then attached to a tree-like polymer called dendrimer which is formed by polyethylene glycol core and surrounding citric acid groups. Stability studies of the drug were carried out to ensure proper synthesis. Then, the uptake of the drug into liver hepatocellular cell line and the drug cytotoxicity were evaluated. Finally, in vitro and in vivo MR imaging were performed with the new synthetic drug. Based on the findings of this research, connecting gadopentetate to dendrimer surface produces a stronger, safer, and more efficient contrast media. Gd(III)-diethylenetriamine pentaacetate-meglumine-dendrimer drug has the ability to enter cells and does not produce significant cytotoxicity. It also increases the relaxivity of tissue and enhances the MR images contrast. The obtained results confirm the hypothesis that the binding of gadopentetate to citric acid dendrimer produces a new, biodegradable, stable, and strong version of the old contrast media.