Labeling of biotin with [166Dy]Dy/166Ho as a stable in vivo generator system.
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.
Ferro-Flores
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G
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
Arteaga de Murphy
C
C
Pedraza-López
M
M
Monroy-Guzmán
F
F
Meléndez-Alafort
L
L
Tendilla
J I
JI
Jiménez-Varela
R
R
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
C400052:DTPA-bis-biotin; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D004419:Dysprosium; D001710:Biotin; D004369:Pentetic Acid; D006695:Holmium