Aptamer-based molecular agents have arrived
Biomarkers built upon aptamers rather than peptides and antibodies offer multiple advantages for molecular imaging and several are currently under development, according to a review published Feb. 13 in the Journal of Nuclear Medicine.
Aptamers are single-stranded DNA or RNA oligonucleotides. The pros and cons of aptamer-based compounds were reviewed by Andrew Z. Wang, MD, and Omid C. Farokhzad, MD, from the department of radiation oncology at Lineberger Comprehensive Cancer Center at Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina–Chapel Hill, in Chapel Hill, N.C.
Agents comprising aptamers are ideal for optical imaging, both in fluorescence- and bioluminescence-based techniques, which allow researchers to peer into physiology at the cellular and molecular level. Aptamer imaging agents have several noted perks over more conventionally used ligands in molecular imaging. These include their small size, which presents the opportunity to go deeper into cellular processes and clear the body more readily. They also can be linked up to fluorescent molecules or nanoparticles for targeted imaging. Aptamer agents are effective biomarkers for a range of nucleic acids, lipids, sugars and proteins selected by systemic evolution of ligands by exponential enrichment (SELEX), a process introduced in 1990. In the body, aptamer agents can pinpoint anatomy and disease-specific anatomy including integrins, nucleolin and prostate-specific membrane antigen (PSMA).
One of the unique qualities of these agents is their ability to mold to a three-dimensional structure on their own. This makes them more stable and less likely to become denatured by antibodies and temperature or pH changes. Antibodies are not so resilient. Also, unlike antibodies, aptamers are synthesized chemically and are less likely to suffer variability in production.
Their diminutive size is both a positive and a negative in terms of clearance. These agents do not tend to remain in the body and this has hampered attempts to develop therapeutic agents, which currently are being designed to unload targeted drug treatments or otherwise modify downstream signaling. Aptamer agents may also become degraded by the presence of nucleases.
These agents are best if not subjected to circulation and are instead introduced locally, such as in ocular injection. The only aptamer agent currently approved by the U.S. Food and Drug Administration is pegaptanib, a biomarker for vascular endothelial growth factor, intrinsic to angiogenesis in age-related macular degeneration.
Future aptamer agents hold promise for inflammation imaging when conjugated with technetium-99m, and may be ideal for tenascin-C protein imaging to target tumor growth and angiogenesis. MUC1 protein may also be a good target for these agents and are implicated in a number of cancer and tumor types, such as breast cancer. One specific study cited involved the nucleolin seeking AS1411 aptamer bound to a cobalt-ferrite nanoparticle featuring fluorescent rhodamine. Together with gallium-67, this radioligand was detectable by fluorescence, MR and nuclear imaging and was effective both in vitro and in vivo. This could be one agent worth watching in the realm of oncologic imaging.