title: Rapid (18)F-labeling and loading of PEGylated gold nanoparticles for in vivo applications.
abstract: Water-soluble 3 nm maleimide-terminated PEGylated gold nanoparticles (maleimide-AuNP) were synthesized in both partially hydrolyzed and nonhydrolyzed forms. Both of these maleimide-AuNPs, when reacted with the silicon-fluorine prosthetic group [(18)F]SiFA-SH, resulted in radiolabeled AuNPs. These NPs were readily purified with high radiochemical yields (RCY) of 60-80% via size exclusion chromatography. Preliminary small animal positron emission tomography (PET) measurements in healthy rats gives information about the pathway of excretion and the stability of the radioactive label in vivo. The partially hydrolyzed [(18)F]SiFA-maleimide-AuNPs shows uptake in the brain region of interest (ROI) (> 0.13%ID/g) which was confirmed by ex vivo examination of the thoroughly perfused rat brain. The multiple maleimide end groups on the AuNP surface also allows for the simultaneous incorporation of [(18)F]SiFA-SH and a bioactive peptide (cysteine-modified octreotate, cys-TATE, which can bind to somatostatin receptor subtypes 2 and 5) in a proof-of-concept study. The well-defined Michael addition reaction between various thiol containing molecules and the multifunctionalized maleimide-AuNPs thus offers an opportunity to develop a new bioconjugation platform for new diagnostics as well as therapeutics.
authors.affiliation: Montreal Neurological Institute & Hospital, McGill University , 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Joshua
authors.initials: J
authors.lastname: Chin
authors.forename: Carmen
authors.initials: C
authors.lastname: Wängler
authors.forename: Bjoern
authors.initials: B
authors.lastname: Wängler
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Lennox
authors.forename: Ralf
authors.initials: R
authors.lastname: Schirrmacher
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D008301:Maleimides / Q000737:chemistry / Q000493:pharmacokinetics; D053768:Metal Nanoparticles / Q000737:chemistry; D015394:Molecular Structure; D017646:Organosilicon Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: C539566:4-(di-tert-butyl(18F)fluorosilyl)benzenethiol; D005462:Fluorine Radioisotopes; D008301:Maleimides; D017646:Organosilicon Compounds; C043592:maleimide; D011092:Polyethylene Glycols; D006046:Gold