[~11C]-METHYLATED LY2181308, AN ANTISENSE OLIGONUCLEOTIDE TO SURVIVIN: RADIOCHEMICAL SYNTHESIS AND PRELIMINARY RODENT BIODISTRIBUTION STUDIES

摘要

Survivin is involved in the control of cell division and in apoptosis by modulation or inhibition of caspases; it is expressed in many human neoplasms and appears to be involved in tumor cell resistance to some anti-cancer agents and ionizing radiation. Survivin has been described to be selectively expressed in the most common human neoplasms and to be associated with clinical tumor progression. Because of all these properties, survivin has been proposed as a promising target for new anticancer treatments. LY2181308 is an 18 mer oligonucleotide with a molecular weight of 6,404 Da designed against survivin mRNA. A number of structural modifications to the sugar and phosphodiester backbone performed to increase its in vivo stability are: introduction of a 2-methoxyethyl ether (into the sugar moiety) and incorporation of phosphothiorioate (into the phosphodiester backbone) respectively.