Abstract 373: Oligonucleotide aptamer: A promising imaging probe for CD30-positive lymphoma tumors
Authors: Zu Youli , Zeng Zihua 
Published: August 2012

Aptamers are a class of small molecule ligands composed of short single-stranded oligonucleotides and able to bind a variety of targets with high affinity and specificity. Although aptamer technology has emerged over the past several decades its potential clinical value has not yet been fully explored. Aptamer probes can be easily generated through chemical synthesis and simply modified with tracking reporters. In addition, aptamers have little or no immunogenicity and thus, are suitable for in vivo use for disease diagnosis and targeting therapy. Lymphomas are cancers originating from the lymphatic system and can be specifically diagnosed by histology examination of tumor tissues. However, none of modern imaging technologies, including CT, MRI, and PET, is specific for in vivo imaging of lymphoma tumors. Notably, a new antibody-mediated CD30-targeting therapy (Brentuximab) has been recently approved by FDA for relapsed CD30-positive lymphomas although no specific imaging method for monitoring of therapeutic response is available up to date. Our previous studies have demonstrated that the synthetic aptamers can be used as probes to specifically diagnose lymphoma cells by multi-color flow cytometry and selectively detect lymphoma in paraffin-embedded tumor tissues by immunohistochemical staining. In this proof-of-concept study, we investigated the aptamers for specific in vivo imaging of CD30-positive lymphoma tumors. For this purpose, the CD30-specfic aptamer probes were chemically synthesized as described previously and conjugated with near-infrared fluorophore IRD800CW reporter. The tumor-bearing mouse model was established to carry both CD30-positive lymphoma and CD30-negative control tumors in each mouse. The CD30 aptamer probes were systemically administrated through the tail vein of the tumor-bearing mice. A whole-body scan by the XENOGEN IVIS 200 Imaging System was carried out. Imaging studies revealed that that the aptamer probes selectively and specifically highlighted the CD30-positive lymphoma tumor, but not the control tumor in the same mouse. The specific imaging signals from aptamers reached the highest peak instantly post administration, gradually diminished to 50% density at 30 min, and disappeared from mouse body within 2 hrs. In addition, systemic distribution study indicated that the aptamer probes were removed from the body mainly through the kidneys and gastro-intestinal system (gallbladder, cecum, and colon). In summary, these findings demonstrate that synthetic aptamers can be used for specific in vivo imaging of lymphoma tumor, providing solid foundation to develop an imaging approach for real-time monitoring of therapeutic response of Brentuximab and early detection of CD30-positive lymphoma relapse.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 373. doi:1538-7445.AM2012-373