Gadofullerene MRI Contrast Agents

Future Perspective

With their special metal-ion chelation unlike that offered by any classic coordination complex, high water-proton relaxivities and their flexible surface functionalization chemistry, gadofullerenes are poised to serve as the platform in a series of diverse new Gd³⁺-based MRI contrast agents. With a better understanding of the relaxivity properties of gadofullerenes, the current research status demands more research and development on several fronts to advance metallofullerenes as contrast agents. Areas that need this continued focus include the manufacture of metallofullerene raw materials, the isolation and characterization of discrete metallofullerene compounds and new conjugation chemistry for the creation of bioactive derivatives. Although the organic chemistry of fullerenes, such as C₆₀, is maturing, metallofullerenes often have different reactivity patterns from their empty counterparts, so there is much room for new enabling derivatization chemistry. Major advances in these various areas will be attained in the near future, which will immediately benefit progression of metallofullerenes as contrast agents and in other biomedical applications. Thus, creation of elaborated agents for specific imaging applications is the area with the most promise for new progress in the next 5-10 years. The recent demonstrations of cellular imaging with gadofullerene derivatives^[33,34] are strong indicators of the potential for exploiting the stable Gd³⁺ encapsulation and high relaxivities in cellular and molecular imaging of diseases, such as cancer (primary and metastatic tumors), and for cardiovascular imaging.

Besides bioconjugation and specific targeting, new derivatives for cellular and molecular imaging will require attention to the agents' osmolality, biodistribution, pharmacokinetics and toxicity. Ideally, the biological properties of gadofullerenes will be manipulated in concert with their relaxivity properties, including maintaining the high relaxivities or even creating an activatable agent that turns on (or off) in response to a particular biological stimulus. Advancement of an entry-level gadofullerene agent to the necessary preclinical and clinical testing stages necessary, prior to approved drug status, may occur before the more advanced applications are fully realized. Outside of MRI, metallofullerenes that encapsulate radioisotopes have the potential to contribute in nuclear medicine applications,^[37] however, it seems that metallofullerene-based MRI contrast agents are well positioned to contribute in a shorter time frame.

Collaboration on gadofullerene contrast agent characterization and development studies with Lon J Wilson of Rice University (Houston, TX, USA) and André E Merbach and Lothar Helm of the École Polytechnique Fédérale de Lausanne (Lausanne, Switzerland) and their students is sincerely appreciated.

Nanomedicine. 2008;3(2):201-213. © 2008  Future Medicine Ltd.

No writing assistance was utilized in the production of this manuscript.

Cite this: Gadofullerene MRI Contrast Agents - Medscape - Mar 01, 2008.