Labeling of biotin with [116Dy]Dy/166Ho as a stable in vivo generator system

The aim of this work was to synthesize [Dy-166]Dy/Ho-166-DTPA-Biotin to evaluate its potential as a new radiopharmaceutical for targeted radiotherapy. Dysprosium-166 (Dy-166) was obtained by neutron irradiation of enriched (Dy2O3)-Dy-164 in a Triga Mark III reactor. The labeling was carried out in aqueous media at pH 8.0 by addition of [Dy-166]DyCl3 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 C for 24 h. The [Dy-166]Dy/Ho-166-labeled biotin was obtained with a 99.1 +/- 0.6% radiochemical purity. In vitro studies demonstrated that [Dy-166]Dy/Ho-166-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 Dy-166 that could produce release of Ho-166(3+). Avidity of labeled biotin for avidin was not affected by the labeling procedure. Biodistribution studies in normal mice showed that the [Dy-166]Dy/Ho-166-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. (C) 2003 Elsevier Science B.V. All rights reserved.