3'-TC-99M-LABELING AND BIODISTRIBUTION OF A CAPL ANTISENSE OLIGODEOXYNUCLEOTIDE

CARL is a cancer related gene shown to be overexpressed during tumor m etastasis 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 radiola beled conjugates in normal mice was studied. A Tc-99m-MAG3-GX-1 comple x of >97% radiochemical purity was obtained and the product was stable for >6 h as determined by reversed phase high performance liquid chro matography (HPLC). Biodistribution studies of the Tc-99m-MAG3-ODNs in groups of four normal mice, sacrificed 5 min and 60 min after injectio n, demonstrated that the radiolabeled ODNs were distributed in an unsp ecific 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-CT RL1 was found in the urine. This finding is clearly different from pre viously 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 degr adation in vivo. (C) 1998 Elsevier Science Inc.