title: Riboflavin carrier protein-targeted fluorescent USPIO for the assessment of vascular metabolism in tumors.
abstract: Riboflavin (Rf) and its metabolic analogs flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are essential for normal cellular growth and function. Their intracellular transport is regulated by the riboflavin carrier protein (RCP), which has been shown to be over-expressed by metabolically active cancer cells. Therefore, FAD-decorated ultrasmall superparamagnetic iron oxide nanoparticles (FAD USPIO) were developed as the first carrier-protein-targeted molecular MR agents for visualizing tumor metabolism. FAD USPIO were synthesized using an adsorptive, fluorescent and non-polymeric coating method, and their physicochemical properties were characterized using TEM, SEM, FTIR, MRI and fluorescence spectroscopy. In vitro analyses showed the biocompatibility of FAD USPIO, and confirmed that they were strongly and specifically taken up by cancer (LnCap) and endothelial (HUVEC) cells. In vivo molecular MRI together with subsequent histological validation finally demonstrated that FAD USPIO efficiently accumulate in tumors and tumor blood vessels, indicating that RCP-targeted diagnostic nanoparticles are interesting new materials for the assessment of vascular metabolism in tumors.
authors.affiliation: Department of Experimental Molecular Imaging, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Jabadurai
authors.initials: J
authors.lastname: Jayapaul
authors.forename: Susanne
authors.initials: S
authors.lastname: Arns
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Lederle
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.forename: Peter
authors.initials: P
authors.lastname: Comba
authors.forename: Jessica
authors.initials: J
authors.lastname: Gätjens
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods; D053758:Nanoparticles; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology
chemical_list: D003911:Dextrans; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; D026901:Membrane Transport Proteins; C097921:ferumoxtran-10; C019079:riboflavin-binding protein; D005182:Flavin-Adenine Dinucleotide