New patent on magnetic resonance imaging (MRI) contrast agents based on organic metal-free dendrimers
Magnetic resonance imaging (MRI) is a commonly used clinical imaging technique for noninvasive diagnosis and characterization of soft tissues. The technique provides images in excellent detail of tumors and related pathological conditions thanks to the contrast agents used in the procedure. Now, a group of researchers from the ICMAB led by José Vidal-Gancedo, from the Nanomol Group, have developed organic metal-free magnetic resonance imaging (MRI) contrast agents based on dendrimers with a totally innovative synthesis procedure.
These new molecules could substitute the common and widely used gadolinium (Gd) based contrast agents, which are considered to be toxic, since Gd (III) ions accumulate in some tissues (brain, bones, kidneys…). Moreover, a relation between their administration and the development of nephrogenic systemic fibrosis is found.
The new dendrimers are excellent candidates for MRI contrast agents suited for biomedical applications, since they are non-toxic and are eliminated from live tissues in hours. Moreover, they are highly soluble on biological fluids and have a long-term contrast activity with a much lower concentration than the Gd-based contrast agents.
These new dendrimers are based on polyphosphorhydrazone (PPH) functionalized with PROXYL radical units. The high water solubility and the anchoring of the radical units on the dendrimer is achieved by using a Tyrosine amino acid (Tyr) linker.
"The importance of using these radical dendrimers comes, not only from the fact that their toxicity is very low, but from their great versatility, since we can modulate their size and physical-chemical properties. In addition, what we are most proud of is to have prepared highly water soluble dendrimers, which required a totally innovative synthesis path” explains José Vidal-Gancedo, principal investigator of the study.
Fully Water-Soluble Polyphosphorhydrazone-Based Radical Dendrimers Functionalized with Tyr-PROXYL Radicals as Metal-Free MRI T1 Contrast Agents. Luiz F. Pinto, Vega Lloveras, Songbai Zhang, Flonja Liko, Jaume Veciana, José L. Muñoz-Gómez, and José Vidal-Gancedo. ACS Appl. Bio Mater. 2020, 3, 369−376. DOI: 10.1021/acsabm.9b00855.
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