Abstract
Purpose
The excellent contrast of high atomic number (Z) elements compared to soft tissues has advanced their use as contrast agents for computed tomographic imaging and as potential radiation sensitizers. We evaluated whether gadolinium (Gd) could serve as such a theranostic agent for high-resolution magnetic resonance imaging (MRI) due to its paramagnetic properties and radiosensitization due to its high Z.
Materials and methods
To improve the relaxivity of Gd, we coupled it to [60]fullerene, an elemental carbon allotropic nanoparticle that seamlessly traverses physiological barriers . By adding serinol, an aliphatic alcohol derived from amino acid serine, we turned [60]fullerene, which is otherwise insoluble in water, into a highly water-soluble derivative and decorated it externally with a payload of chelated gadolinium ions.
Results
When [60]fullerene was functionalized in this manner with two gadolinium ions (Gd2C60), it displayed considerably higher T1 relaxivity at 4.7 T than the commercially used MRI contrast agent, Magnevist, (18.2 mM−1s−1 vs. 4.7 mM−1s−1). Attempts to increase this even further via decoration of [60]fullerene with 12 gadolinium ions was unsuccessful due to a poor water solubility. However, the current formulation of Gd2C60 did not result in any appreciable radiosensitization.
Conclusion
Our results show a successful generation of a novel contrast agent via decoration of fullerene with two chelated Gd ions. Though this formulation was not successful in generating radiosensitization, other chemical modifications can be further explored to increase radiosensitization potential.
Acknowledgements
The authors acknowledge support from the Center for Radiation Oncology Research at MD Anderson Cancer Center for ICP-MS studies at the Chemical Imaging Core facility.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
Notes on contributors
Joseph Byung-Kyu Kim
Joseph Byung-Kyu Kim is currently an MD/PhD student in Dr. Krishnan's group doing his PhD in therapeutics and pharmacology at the University of Texas MD Anderson Cancer Center-the University of Texas Health Graduate School of Biomedical Sciences and McGovern Medical School. His research interests lie in designing and testing out nanoparticles for cancer therapeutics, including gold (AuNPs) and [60] fullerene. Currently he is working on designing and synthesizing novel, high efficacy MRI gadolinium-based contrast agents with the purpose of reducing the Gd ion leakage in vivo.
Yuri Mackeyev
Yuri Mackeyev received his PhD from Lomonosov Moscow State University for the synthesis and study of properties of fluorinated [60] fullerenes. Presently he is an Assistant Professor in Dr. Krishnan's group at Mayo Clinic Florida. His research interests lie in an interdisciplinary area between organic chemistry, chemistry of nanomaterials and clinical cancer research. These include a multibranch effort to define fundamental mechanisms and targets for cancer treatment with ionizing radiation using metal nanoparticles and protection of normal tissues from radiation injury with [60]fullerenes and efficiently translate them to effective innovations for patients. He has published over 40 manuscripts, mainly focused on medical application of nanomaterials, including gold (AuNPs), carbon nanotubes (CNTs), graphene nanoribbons (GNRs), [60] fullerene and fluorescently-tagged polymeric composites.
Subhiksha Raghuram
Subhiksha Raghuram is a Medical Graduate currently working in Dr. Cho's group at The University of Texas MD Anderson Cancer Center. Her research interests are primarily in bioinformatics, interrogation of immune biology of tumors, and evaluation of novel strategies to home nanoparticles to tumors.
Sang Hyun Cho
Sang Hyun Cho, PhD currently holds the position of Professor in Radiation Physics and Imaging Physics at The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sunil Krishnan
Sunil Krishnan is a Professor of radiation oncology at Mayo Clinic Florida with a laboratory focus on strategies to sensitize tumors to radiation therapy and protect normal tissues from radiation therapy using chemotherapy agents, botanicals, immunotherapy agents, and nanoparticles.