title: Labeling of biotin with [166Dy]Dy/166Ho as a stable in vivo generator system.
abstract: The aim of this work was to synthesize [166Dy]Dy/166Ho-DTPA-Biotin to evaluate its potential as a new radiopharmaceutical for targeted radiotherapy. Dysprosium-166 (166Dy) was obtained by neutron irradiation of enriched 164Dy(2)O(3) in a Triga Mark III reactor. The labeling was carried out in aqueous media at pH 8.0 by addition of [166Dy]DyCl(3) to diethylenetriaminepentaacetic-alpha,omega-bis(biocytinamide) (DTPA-Biotin). Radiochemical purity was determined by high-performance liquid chromatography (HPLC) and TLC. The biological integrity of labeled biotin was studied evaluating its avidity for avidin in an agarose column and by size-exclusion HPLC analysis of the radiolabeled DTPA-Biotin with and without the addition of avidin. Stability studies against dilution were carried out by diluting the radiocomplex solution with saline solution and with human serum at 37 degrees C for 24 h. The [166Dy]Dy/166Ho-labeled biotin was obtained with a 99.1+/-0.6% radiochemical purity. In vitro studies demonstrated that [166Dy]Dy/166Ho-DTPA-Biotin is stable after dilution in saline and in human serum and no translocation of the daughter nucleus occurs subsequent to beta(-) decay of 166Dy that could produce release of 166Ho(3+). Avidity of labeled biotin for avidin was not affected by the labeling procedure. Biodistribution studies in normal mice showed that the [166Dy]Dy/166Ho-DTPA-Biotin has a high renal clearance. In conclusion, the radiolabeled biotin prepared in this investigation has adequate properties to work as a stable in vivo generator system for targeted radiotherapy.
authors.affiliation: Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Km. 36.5 Carretera México-Toluca, Ocoyoacac, Estado de México, C.P. 52045, Mexico. gff@nuclear.inin.mx
authors.forename: G
authors.initials: G
authors.lastname: Ferro-Flores
authors.forename: C
authors.initials: C
authors.lastname: Arteaga de Murphy
authors.forename: M
authors.initials: M
authors.lastname: Pedraza-López
authors.forename: F
authors.initials: F
authors.lastname: Monroy-Guzmán
authors.forename: L
authors.initials: L
authors.lastname: Meléndez-Alafort
authors.forename: J I
authors.initials: JI
authors.lastname: Tendilla
authors.forename: R
authors.initials: R
authors.lastname: Jiménez-Varela
mesh_terms: D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004355:Drug Stability; D004419:Dysprosium / Q000737:chemistry*; D005260:Female; D006695:Holmium / Q000737:chemistry*; D007275:Injections, Intravenous; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D011868:Radioisotopes / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C400052:DTPA-bis-biotin; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D004419:Dysprosium; D001710:Biotin; D004369:Pentetic Acid; D006695:Holmium