3′-99mTc-labeling and biodistribution of a CAPL antisense oligodeoxynucleotide

CARL is a cancer related gene shown to be overexpressed during tumor metastasis formation. A CAPL antisense oligodeoxynucleotide (ODN), GX-I, and a random control ODN (CTRL1) were 3'-conjugated to MAG3, labeled with technetium-99m, purified, and the biodistribution of the radiolabeled conjugates in normal mice was studied. A Tc-99m-MAG3-GX-1 complex of >97% radiochemical purity was obtained and the product was stable for >6 h as determined by reversed phase high performance liquid chromatography (HPLC). Biodistribution studies of the Tc-99m-MAG3-ODNs in groups of four normal mice, sacrificed 5 min and 60 min after injection, demonstrated that the radiolabeled ODNs were distributed in an unspecific manner. The excretion route was mainly urinary. At 60 min, 55.2% of the injected dose of Tc-99m-MAG3-GX-1 and 72.4% of Tc-99m MAG3-CTRL1 was found in the urine. This finding is clearly different from previously reported data on tritiated 20-mer phosphodiester ODNs, as well as the unconjugated Tc-99m-MAG3 chelate, suggesting that Tc-99m-MAG3 coupled to the 3'-end of ODNs has an influence on the biodistribution of the oligo, and possibly has a protective function to enzymatic degradation in vivo. (C) 1998 Elsevier Science Inc.