title: Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung.
abstract: Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the ​in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a 'proof-of-concept' experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA. Electronic address: semurphy@wakehealth.edu.
authors.forename: Sean V
authors.initials: SV
authors.lastname: Murphy
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA. Electronic address: halear0@gmail.com.
authors.forename: Austin
authors.initials: A
authors.lastname: Hale
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA. Electronic address: tareid@wakehealth.edu.
authors.forename: Tanya
authors.initials: T
authors.lastname: Reid
authors.affiliation: Center for Biomolecular Imaging, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. Electronic address: jdolson3@earthlink.net.
authors.forename: John
authors.initials: J
authors.lastname: Olson
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA. Electronic address: akidiyoo@wakehealth.edu.
authors.forename: Amritha
authors.initials: A
authors.lastname: Kidiyoor
authors.affiliation: Center for Biomolecular Imaging, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. Electronic address: jtan@wakehealth.edu.
authors.forename: Josh
authors.initials: J
authors.lastname: Tan
authors.affiliation: Luna nanoWorks Division, Luna Innovations, Incorporated, Danville, VA 24541, USA. Electronic address: zhouz@lunainc.com.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA. Electronic address: jojackso@wakehealth.edu.
authors.forename: John
authors.initials: J
authors.lastname: Jackson
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA. Electronic address: aatala@wakehealth.edu.
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D058948:Cell Tracking; D002478:Cells, Cultured; D003287:Contrast Media / Q000737:chemistry* / Q000633:toxicity; D037741:Fullerenes / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D057230:Limit of Detection; D008168:Lung / Q000000981:diagnostic imaging* / Q000473:pathology; D055370:Lung Injury / Q000000981:diagnostic imaging* / Q000628:therapy; D008279:Magnetic Resonance Imaging; D000075163:Metallocenes; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019047:Phantoms, Imaging; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging* / Q000628:therapy; D013194:Staining and Labeling; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology
chemical_list: D003287:Contrast Media; D037741:Fullerenes; D000075163:Metallocenes; C000613259:Trimetasphere
keywords: Cell tracking; Contrast agent; Endohedral metallofullerenes; Gadolinium; Lung disease; Magnetic resonance imagining