Conjugation to Biocompatible Dendrimers Increases Lanthanide T2 Relaxivity of Hydroxypyridinone Complexes for Magnetic Resonance Imaging

• Published in: European journal of inorganic chemistry Vol. 2012; no. 12; pp. 2108 - 2114
• Main Authors: Klemm, Piper J., Floyd III, William C., Andolina, Christopher M., Fréchet, Jean M. J., Raymond, Kenneth N.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-04-2012; WILEY‐VCH Verlag
• Subjects: Conjugation; Dendrimers; Imaging agents; Lanthanides; MRI probes
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.201101167

Magnetic resonance imaging (MRI) contrast agents represent a worldwide billion‐dollar market annually. While T1 relaxivity enhancement contrast agents receive greater attention and a significantly larger market share, the commercial potential for T2 relaxivity enhancing contrast agents remains a viable diagnostic option because of their increased relaxivity at high field strengths. Improvement of the contrast and biocompatibility of T2 MRI probes may enable new diagnostic prospects for MRI. Paramagnetic lanthanides have the potential to decrease T1 and T2 proton relaxation times, but are not commercially used in MRI diagnostics as T2 agents. In this article, oxygen donor chelates (hydroxypyridinone, HOPO, and terephthalamide, TAM) of various lanthanides are demonstrated as biocompatible macromolecular dendrimer conjugates for the development of T2 MRI probes. These conjugates have relaxivities of up to 374 mM–1 s–1 per dendrimer, high bioavailability, and low in vitro toxicity.
The development of high relaxivity andbiofunctional MRI probes is essential to increasing clinical diagnostic ability. T2 MRI probes using lanthanides have the potential to increase relaxivity, biocompatibility, and offer the prospective to increase imaging modality functions.