Labeling of biotin with [formula omitted]/ [formula omitted] as a stable in vivo generator system

Abstract

The aim of this work was to synthesize [ 166 Dy] Dy / 166 Ho -DTPA-Biotin to evaluate its potential as a new radiopharmaceutical for targeted radiotherapy. Dysprosium-166 ( 166 Dy ) was obtained by neutron irradiation of enriched 164 Dy 2 O 3 in a Triga Mark III reactor. The labeling was carried out in aqueous media at pH 8.0 by addition of [ 166 Dy] DyCl 3 to diethylenetriaminepentaacetic-α,ω-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 °C for 24 h. The [ 166 Dy] Dy / 166 Ho -labeled biotin was obtained with a 99.1±0.6% radiochemical purity. In vitro studies demonstrated that [ 166 Dy] Dy / 166 Ho -DTPA-Biotin is stable after dilution in saline and in human serum and no translocation of the daughter nucleus occurs subsequent to β − decay of 166 Dy that could produce release of 166 Ho 3+ . Avidity of labeled biotin for avidin was not affected by the labeling procedure. Biodistribution studies in normal mice showed that the [ 166 Dy] Dy / 166 Ho -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.