In The July Issue
- Meet with Pair in Boston
- Base Pair Welcomes Garam Lee
- In Vivo Imaging with Aptamers
Meet with Base Pair in Boston
Coming to Boston for the Bioprocessing Summit August 13-17? Set up a meeting with a Base Pair aptamer specialist to learn more about aptamers for process optimization / small molecule quantification, detection of contaminants, and affinity purification.
Base Pair Welcomes Garam Lee
Base Pair is pleased to welcome Garam Lee to the Base Pair scientific team. Garam has a B.S. and M.S. in genetic engineering from Suwon University in Korea. She worked on the International Rice Genome Project at Seoul National University, where she earned her Ph.D. Garam developed and patented a 2’F RNA aptamer against PCV2 viral capsid at the Veterinary CDC in Korea. She also developed in vivo and cell-based DNA aptamers at M.D. Anderson Cancer Center and developed a 2’F RNA aptamer against NMDA receptor from glutamate receptors in neurons at the University of Texas Medical School. “I’m excited to be working on some new and interesting aptamer projects at Base Pair.” – Garam
In Vivo Imaging with Aptamers
Imaging plays a major role in the diagnosis and monitoring of disease. For some cancers, including lung cancer, pancreatic cancer, and liver cancer, earlier detection through more sensitive imaging is needed to accelerate treatment and improve outcomes (2). In an effort to increase the sensitivity of in vivo imaging, several research groups are currently working with aptamers for targeted imaging.
Aptamers are small, single-stranded oligonucleotides with selectivity and affinity properties similar to antibodies. Due to their small size, aptamers are generally non-immunogenic and penetrate tumor tissue more quickly and easily. They are chemically synthesized and easily modified for detection and enhanced in vivo stability (Read “Enhancing Aptamer Stability”). They can be selected to differentiate between highly similar compounds and conjugated to a wide range of molecules without affecting target binding. Selectivity, biocompatibility and flexibility make aptamers ideal targeting agents for in vivo imaging (1).
Aptamer-Mediated Near-Infrared (NIR) Imaging
Researchers at Fudan University in China recently selected an aptamer to GPC3, a cell surface protein that is highly expressed in hepatocellular carcinoma (HCC) tissue, the most common type of liver cancer. Aptamer AP613-1 was shown to selectively target Huh-7 (GPC3+) HCC cells vs. A549 lung cancer cells in vitro. The aptamer was labeled with Alexa Fluor™ 750, a near-infrared dye, and used to image subcutaneous Huh-7 HCC tumors in nude mice both in vivo and ex vivo. Experimental and control mice showed similar levels of fluorescence in major organs, but the experimental group showed elevated levels of fluorescence at the tumor site, showing successful aptamer targeting (2).
Average fluorescence intensities were approximately 20-30% higher when organs were imaged ex vivo compared with in vivo imaging, but the results showed strong correlation (correlation coefficient of 0.968). The in vivo imaging data accurately showed the bio-distribution of the imaging agent in major organs. Data also showed that selective aptamers can be used to detect subcutaneous tumors via NIR fluorescence imaging, making it possible to monitor tumor response in an animal model in vivo, without sacrificing the animal. Aptamer complexing with magnetic nanoparticles or 18F would enable enhanced imaging via MRI or PET-CT for early detection and monitoring of deep-tissue tumors (2).
Aptamer Targeting in Magnetic Resonance Imaging (MRI)
Magnetic Resonance Imaging (MRI) is a non-invasive imaging technology known for superior spatial resolution and contrast in soft tissue (1,3). Traditional small molecule imaging agents used in MRI offer limited contrast enhancement, as binding is non-specific and agents are rapidly cleared. Specific antibodies have been used as targeting agents, but have difficulty diffusing into tumor tissue and are rapidly cleared by the body’s reticuloendothelial system (1). A growing number of researchers are overcoming these limitations with aptamers.
Researchers at JiangSu University in China selected an aptamer against hypoxia-inducible factor-1α (HIF-1α) for enhanced imaging of hypoxia-induced cancer stem cells, believed to play an important role in cancer metastasis, therapy resistance, and tumor recurrence. PEG- and Mn(II)-modified magnetic nanoparticles were bound to the HIF-1α aptamer and evaluated in MRI both in vitro and in vivo. In vitro imaging of Panc-1 and Bxpc-3 pancreatic carcinoma cell lines showed a 7-fold increase in signal with aptamer targeting. In vivo imaging of a xenograft of Panc-1 in a mouse model showed a 3.5-fold increase in signal with aptamer targeting. Histopathological examination of major organs showed no toxic effects from the nanoparticles. The biocompatible aptamer-nanoparticles successfully targeted cancer cells in hypoxic regions and significantly enhanced signal and contrast in MRI. Aptamer-targeting can be applied to a wide range of imaging applications, from preclinical research to drug development and distribution studies to early detection and treatment monitoring for many forms of cancer.
Aptamer Selection for In Vivo Imaging
Aptamers can be selected for targeting of specific cell surface markers or specific cell types (without a known surface marker) for non-invasive detection and monitoring. Aptamers can be selected for targeting of metabolites and synthetic small molecules to facilitate the study of bio-distribution, drug metabolism, and drug clearance. Base Pair’s patented multiplex SELEX technology enables simultaneous selection of aptamers to several targets, decreasing the time and cost of aptamer development. Aptamer development can include modification for enhanced stability and conjugation to a wide range of linkers and imaging agents.
Contact Base Pair today for more information on selection of aptamers for in vivo imaging.
1. Zhang, Y. et al. Aptamer-targeted magnetic resonance imaging contrast agents and their applications. Journal of Neuroscience and Nanotechnology. 2018. 18:3759-3774.
2. Zhao, M., et al. In vivo fluorescence imaging of hepatocellular carcinoma using a novel GPC3-specific aptamer probe. Quantitative Imaging in Medicine and Surgery. 2018. 8(2) :151-160.
3. Zhu, H., et al. Aptamer-PEG-modified Fe3O4@Mn as a novel T1- and T2- dual-model MRI contrast agent targeting hypoxia-induced cancer stem cells. Nature: Scientific Reports. 2016. 6:39245.