Novel membrane-permeable contrast agent for brain tumor detection by MRI.
One of the key challenges hindering the clinical intervention against brain cancer is defined by the inability to detect brain tumors at an early enough stage to permit effective therapy. Furthermore, the rapid growth and severe lethality of this form of cancer predicate the vital importance of monitoring the development of the pathology and its outcome after therapeutic intervention. With this in mind, we designed a novel membrane-permeant contrast agent, MN-MPAP-Cy5.5, which consists of a superparamagnetic iron oxide core, for MRI conjugated to myristoylated polyarginine peptides, as a membrane translocation module and labeled with the near-infrared dye Cy5.5 for correlative microscopy. This probe showed a remarkable uptake by U-87 human glioma cells in vitro and localized and delineated stereotactically injected tumor in vivo by MRI. Our findings suggest that the agent mediates its effects by translocation of the magnetic nanoparticles label across the leaky tumor vasculature, followed by enhanced accumulation in tumor cells. The noninvasive detection of brain tumors when they are still small represents a formidable challenge from an imaging standpoint. Our study describes an improved strategy to detect brain lesions by utilizing a contrast agent with membrane translocation properties.
Kumar
Mohanraja
M
Athinoula A. Martines Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA.
Medarova
Zdravka
Z
Athinoula A. Martines Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA.
Pantazopoulos
Pamela
P
Athinoula A. Martines Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA.
Dai
Guangping
G
Athinoula A. Martines Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA.
Moore
Anna
A
Athinoula A. Martines Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA.
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D005290:Ferric Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D015552:Injections, Intralesional; D051379:Mice; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide