title: MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA.
abstract: Detection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in glioma, can be used as a target moiety. We hypothesized that liposomes conjugated with IL-13 and encapsulating MRI contrast agent are capable of passing through an intact BBB and producing MRI contrast with greater sensitivity.
  
  
  
  The targeted MRI contrast agent was created by encapsulating Magnevist (Gd-DTPA) into liposomes conjugated with IL-13 and characterized by particle size distribution, cytotoxicity, and MRI relaxivity. MR image intensity was evaluated in the brain in normal mice post injection of Gd-DTPA and IL-13-liposome-Gd-DTPA one day apart. The specificity for glioma detection by IL-13-liposome-Gd-DTPA was demonstrated in an intracranial glioma mouse model and validated histologically.
  
  
  
  The average size of IL-13-liposome-Gd-DTPA was 137 ± 43 nm with relaxivity of 4.0 ± 0.4 L/mmole-s at 7 Tesla. No significant cytotoxicity was observed with MTS assay and serum chemistry in mice. The MRI signal intensity was enhanced up to 15% post injection of IL-13-liposome-Gd-DTPA in normal brain tissue following a similar time course as that for the pituitary gland outside of the BBB. MRI enhanced by IL-13-liposome-Gd-DTPA detected small tumor masses in addition to those seen with Magnevist-enhanced MRI.
  
  
  
  IL-13-liposome-Gd-DTPA is able to pass through the uncompromised BBB and detect an early stage glioma that cannot be seen with conventional contrast-enhanced MRI.
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: Achuthamangalam B
authors.initials: AB
authors.lastname: Madhankumar
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: Patti A
authors.initials: PA
authors.lastname: Miller
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: Kari A
authors.initials: KA
authors.lastname: Duck
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: Susan
authors.initials: S
authors.lastname: Hafenstein
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: Elias
authors.initials: E
authors.lastname: Rizk
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: Becky
authors.initials: B
authors.lastname: Slagle-Webb
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: Jonas M
authors.initials: JM
authors.lastname: Sheehan
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
authors.affiliation: Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., A.B.M., K.A.D., E.R., B.S.-W., J.M.S., J.R.C., Q.X.Y.); Department of Radiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (X.L., P.A.M., Q.X.Y.); Department of Microbiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania (S.H.).
authors.forename: Qing X
authors.initials: QX
authors.lastname: Yang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D003287:Contrast Media / Q000494:pharmacology*; D004195:Disease Models, Animal; D019786:Gadolinium DTPA / Q000494:pharmacology*; D005910:Glioma / Q000000981:diagnostic imaging*; D018793:Interleukin-13 / Q000494:pharmacology*; D008081:Liposomes / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice
chemical_list: D003287:Contrast Media; D018793:Interleukin-13; D008081:Liposomes; D019786:Gadolinium DTPA
keywords: IL-13; blood-brain barrier (BBB); glioma; liposome; targeted MRI contrast agent