Labeling of biotin with [166Dy]Dy/166Ho as a stable in vivo generator system

• Published in: International journal of pharmaceutics 2003-04, Vol.255 (1-2), p.129-138
• Main Authors: FERRO-FLORES, G, DE MURPHY, C. Arteaga, PEDRAZA-LOPEZ, M, MONROY-GUZMAN, F, MELENDEZ-ALAFORT, L, TENDILLA, J. I, JIMENEZ-VARELA, R
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biotin - analogs & derivatives; Biotin - blood; Biotin - chemistry; Biotin - pharmacokinetics; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Contrast media. Radiopharmaceuticals; Drug Stability; Dysprosium - chemistry; Female; Holmium - chemistry; Injections, Intravenous; Isotope Labeling; Medical sciences; Mice; Mice, Inbred BALB C; Pentetic Acid - analogs & derivatives; Pentetic Acid - blood; Pentetic Acid - chemistry; Pentetic Acid - pharmacokinetics; Pharmacology. Drug treatments; Radioisotopes - chemistry; Radiopharmaceuticals - blood; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Tissue Distribution
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(03)00052-8

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.