title: Radiolabeling of poly(lactic-co-glycolic acid) (PLGA) nanoparticles with biotinylated F-18 prosthetic groups and imaging of their delivery to the brain with positron emission tomography.
abstract: The avidin-biotin interaction permits rapid and nearly irreversible noncovalent linkage between biotinylated molecules and avidin-modified substrates. We designed a biotinylated radioligand intended for use in the detection of avidin-modified polymer nanoparticles in tissue with positron emission tomography (PET). Using an F-18 labeled prosthetic group, [(18)F]4-fluorobenzylamine, and a commercially available biotin derivate, NHS-PEG4-biotin, [(18)F]-fluorobenzylamide-poly(ethylene glycol)4-biotin ([(18)F]NPB4) was prepared with high purity and specific activity. The attachment of the [(18)F]NPB4 radioligand to avidin-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles was tested by using PET imaging to measure the kinetics of convection-enhanced delivery (CED) of nanoparticles of varying size to the rat brain. PET imaging enabled the direct observation of nanoparticle delivery by measurement of the spatial volume of distribution of radiolabeled nanoparticles as a function of time, both during and after the infusion. This work thus validates new methods for radiolabeling PEG-biotin derivatives and also provides insight into the fate of nanoparticles that have been infused directly into the brain.
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine , New Haven, Connecticut 06510, United States.
authors.forename: Rachael W
authors.initials: RW
authors.lastname: Sirianni
authors.forename: Ming-Qiang
authors.initials: MQ
authors.lastname: Zheng
authors.forename: Toral R
authors.initials: TR
authors.lastname: Patel
authors.forename: Thomas
authors.initials: T
authors.lastname: Shafbauer
authors.forename: Jiangbing
authors.initials: J
authors.lastname: Zhou
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D001360:Avidin / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D001921:Brain / Q000187:drug effects; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006207:Half-Life; D007553:Isotope Labeling; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D049268:Positron-Emission Tomography / Q000379:methods*; D017207:Rats, Sprague-Dawley
chemical_list: D005462:Fluorine Radioisotopes; D001360:Avidin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D001710:Biotin