Preparation and preliminary evaluation of a biotin-targeted, lectin-targeted dendrimer-based probe for dual-modality magnetic resonance and fluorescence imaging.
A novel approach for the preparation of a biotinylated dendrimer-based MRI agent 5 is described, in which a unique disulfide bond in the core of the Gd(III)-1B4M-DTPA chelated G2 PAMAM dendrimer was reduced and then attached to a maleimide-functionalized biotin. The new MRI agent 5 features a well-defined dendron structure and a unique biotin functionality. Immobilization of up to four copies of biotinylated dendrimer 5 to fluorescently labeled avidin yields a supramolecular avidin-biotin-dendrimer-Gd(III) complex. Validation of the complex in mice bearing ovarian cancer tumors demonstrates that the avidin-biotin-dendrimer targeting system efficiently targets and delivers sufficient amounts of chelated Gd(III) and fluorophores (e.g., Rhodamine green) to ovarian tumors to produce visible changes in the tumors by both MRI and optical imaging, respectively. Thus, the avidin-biotin-dendrimer complex may be used as a tumor-targeted probe for dual-modality magnetic resonance and fluorescence imaging.
Xu
Heng
H
Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1088, USA.
Regino
Celeste A S
CA
Koyama
Yoshinori
Y
Hama
Yukihiro
Y
Gunn
Andrew J
AJ
Bernardo
Marcelino
M
Kobayashi
Hisataka
H
Choyke
Peter L
PL
Brechbiel
Martin W
MW
D000818:Animals; D001710:Biotin / Q000737:chemistry*; D002614:Chelating Agents / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D005260:Female; D005453:Fluorescence; D005682:Gadolinium / Q000737:chemistry; D007089:Image Enhancement / Q000379:methods*; D037102:Lectins / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D010051:Ovarian Neoplasms / Q000473:pathology; D012235:Rhodamines / Q000737:chemistry; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D002614:Chelating Agents; D050091:Dendrimers; D037102:Lectins; D012235:Rhodamines; D001710:Biotin; D005682:Gadolinium