[11C]Methylated LY2181308

Excerpt

Survivin is a small protein (142 amino acids, 16.5 kDa) that belongs to the inhibitor of apoptosis protein (IAP) family (1). IAPs can effectively suppress apoptosis induced by a variety of stimuli, including death receptor activation, growth factor withdrawal, ionizing radiation, viral infection, and genotoxic damage. Survivin comprises a single baculovirus IAP repeat domain and an extended COOH-terminal α-helical coiled-coil domain but lacks the RING-finger domain found in other IAPs. In addition to suppressing apoptosis, survivin is involved in many essential cellular functions, such as cell division, cell stress response, and surveillance checkpoints. Survivin is strongly expressed in the majority of human tumor types (2). As a new target in cancer treatment, inhibition of survivin expression can be carried out through the use of anti-sense oligonucleotides, ribozymes, and small interfering RNA (3). LY2181308 is an 18-mer survivin anti-sense oligonucleotide (6.8 kDa) against survivin mRNA (4, 5). Dence et al. (6) developed a rapid method for randomly ¹¹C-methylated LY2181308 ([¹¹C]LY2181308) for positron emission tomography (PET) imaging of survivin mRNA expression in tumors.