Evaluation of brain tumor vessels specific contrast agents for glioblastoma imaging.
A mouse model of glioblastoma multiforme was used to determine the accumulation of a targeted contrast agent in tumor vessels. The contrast agent, consisting of superparamagnetic iron oxide coated with dextran, was functionalized with an anti-insulin-like-growth-factor binding protein 7 (anti-IGFBP7) single domain antibody. The near infrared marker, Cy5.5, was also attached for an in vivo fluorescence study. A 9.4T magnetic resonance imaging (MRI) system was used for in vivo studies on days 10 and 11 following tumor inoculation. T(2) relaxation time was used to measure the accumulation of the contrast agent in the tumor. Changes in tumor to brain contrast because of active targeting were compared with a nontargeted contrast agent. Effective targeting was confirmed with near infrared measurements and fluorescent microscopic analysis. The results showed that there was a statistically significant (P < .01) difference in normalized T(2) between healthy brain and tumor tissue 10 min, 1 h, and 2 h point postinjection of the anti-IGFBP7 single domain antibody targeted and nontargeted iron oxide nanoparticles. A statistical difference remained in animals treated with targeted nanoparticles 24 h postinjection only. The MRI, near infrared imaging, and fluorescent microscopy studies showed corresponding spatial and temporal changes. We concluded that the developed anti-IGFBP7-iron oxide single domain antibody-targeted MRI contrast agent selectively binds to abnormal vessels within a glioblastoma. T(2)-weighted MRI and near infrared imaging are able to detect the targeting effects in brain tumors.
Institute for Biodiagnostics (West), National Research Council of Canada, Calgary, Alberta, Canada. boguslaw.tomanek@nrc.ca
Boguslaw
B
Tomanek
Umar
U
Iqbal
Barbara
B
Blasiak
Abedelnasser
A
Abulrob
Homam
H
Albaghdadi
John R
JR
Matyas
Dragana
D
Ponjevic
Garnette R
GR
Sutherland
D000818:Animals; D000906:Antibodies; D001932:Brain Neoplasms / Q000098:blood supply / Q000175:diagnosis*; D045744:Cell Line, Tumor; D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D005909:Glioblastoma / Q000098:blood supply / Q000175:diagnosis*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D053758:Nanoparticles
D000906:Antibodies; D003287:Contrast Media; D003911:Dextrans; D005290:Ferric Compounds; D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1; C000499:ferric oxide