Sgc8-c Aptamer as a Potential Theranostic Agent for Hemato-Oncological Malignancies

Abstract

<b><i>Background:</i></b> Aptamers represent an emerging class of oligonucleotides that have the ability to bind ligands with high affinity. Sgc8-c aptamer recognizes PTK7, a member of the catalytically defective receptor protein tyrosine kinase family that is upregulated in various cancers, including hemato-oncological malignancies. Herein, an Sgc8-c-NOTA-radiolabeled probe was prepared for theranostic purpose. <b><i>Materials and Methods:</i></b> In this work, an Sgc8-c-radiolabeled probe against PTK7 was prepared, and biological evaluations-pharmacokinetic studies, biodistribution analysis, and <i>in vivo</i> molecular imaging-were performed. To obtain the radiolabeled probe, a modified 5'-amino-derivative of the Sgc8-c aptamer was bound to the metal chelator NOTA, and subsequently labeled with ⁶⁷Ga with high yield and radiochemical purity. The precursor, Sgc8-c-NOTA, the radio probe Sgc8-c-NOTA-⁶⁷Ga, and its nonradioactive complex, Sgc8-c-NOTA-^69/71Ga, were purified by reverse-phase high-performance liquid chromatography and characterized by electrospray ionization mass spectrometry. The binding ability of Sgc8-c-NOTA-⁶⁷Ga was studied <i>in vitro</i> against purified PTK7 receptor. In addition, the binding was also evidenced against the hemato-oncological A20 cell line, derived from B lymphocytes, and the corresponding A20-green fluorescent protein (GFP)-transfected cells. The proof of concept was performed on A20-GFP tumor-bearing mice, in which the biodistribution of the radiolabeled probe was evaluated through imaging, using X-ray, fluorescence, and γ modalities. The specific uptake of the probe was confirmed by blocking with the Sgc8-c aptamer in an <i>in vivo</i> competition assay. <b><i>Results:</i></b> The biodistribution results showed considerable uptake in tumor since 2 h, with highest at 48 h postinjection. However, the blood and muscle ID/g (injected dose per gram of tissue) activities were decreasing with time and tumor/no-target ratios increasing to 20 at 24 h postinjection. These results are consistent with the <i>in vivo</i> images. <b><i>Conclusions:</i></b> This study supports the utility of Sgc8-c-NOTA radiolabeled as a theranostic agent.