Potential of mirror-image oligonucleotides as molecular probes for pretargeting

To explore the potential of complementary mirror-image oligonucleotides as recognition systems for pretargeting, the present work deals with radiopharmacological evaluation of an ⁸⁶Y-labeled 17mer l-DNA and of a hybrid consisting of the radiolabeled l-DNA and a complementary l-RNA (Figure 1). The 17mer l-DNA was functionalized with DOTA-Nhydroxysuccinimide ester and radiolabeled with ⁸⁶Y (t_1/2 = 14.7 h) resulting in the HPLCpurified [⁸⁶Y-DOTA]-17mer (31 MBq; 2.0 GBq/μmol). Biodistribution studies with [⁸⁶Y-DOTA]-17mer in Wistar rats showed high renal excretion and moderate kidney uptake (SUV: 18 ± 2.4, 18 h p. i.). More than 87% of [⁸⁶Y-DOTA]-17mer were found intact in rat urine 60 min after injection. In thermal denaturation studies, a high melting point of 68°C (32 mM [Na⁺]) was determined for the hybrid. In conclusion, the high metabolic stability of the l-DNA and the high thermal stability of the l-DNA/l-RNA hybrid suggest the potential of this class of compounds as molecular probes for pretargeting.