In Vivo Evaluation of Sgc8-c Aptamer as a Molecular Imaging Probe for Colon Cancer in a Mouse Xenograft Model.

Ana Paula Arévalo,Manuel Ibarra,Victoria Calzada,Romina Castelli,Martina Crispo

doi:10.3390/ijms23052466

Ana Paula Arévalo, Manuel Ibarra + Show 3 more

Open Access

https://doi.org/10.3390/ijms23052466

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Abstract

Recent biotechnological applications in the field of clinical oncology led to the identification of new biomarkers as molecular targets of cancer, and to broad developments in the field of personalized medicine. Aptamers are oligonucleotides (ssDNA or RNA) that are selected to specifically recognize a molecular target with high affinity and specificity. Based on this, new horizons for their use as molecular imaging probes are being explored. The objective of this work was to evaluate the Sgc8-c aptamer conjugated with Alexa Fluor 647 fluorophore as an imaging probe in a colon tumor xenograft mouse model, with potential application in molecular imaging. In this study, the LS174T cell line was used to induce colorectal adenocarcinoma in nude mice. After confirmation of PTK7 overexpression by immunohistochemistry, in vivo studies were performed. Pharmacokinetic, in vivo and ex vivo biodistribution imaging, and a competition assay were evaluated by fluorescence imaging. In vivo visualization of the probe in the tumors was assessed two hours after aptamer probe administration, exhibiting excellent tumor-to-background ratios in biodistribution studies and high specificity in the competition test. Our results demonstrated the functionality of Scg8-c as an imaging probe for colon cancer, with potential clinical applications.

Highlights

The five types of cancer that cause the highest number of deaths in 2020 were lung (1.8 million), colorectal (935,000), liver (830,000), gastric (769,000), and breast (685,000)
Optical imaging windows exist in the 600–1000 nm area (near-infrared (NIR)) of the electromagnetic spectrum where light absorption of biological molecules is minimal
The objective of this work was to evaluate the performance of Sgc8-c aptamer linked to Alexa Fluor 647 in a mouse xenograft model of colon adenocarcinoma, as an in vivo imaging probe

Summary

Introduction

According to a World Health Organization report from 2020, cancer is one of the principal causes of death, with 10 million deaths in 2021 [1]. Recent advances in imaging technology have positioned this kind of research at the forefront of scientific studies of the diagnosis and evaluation of diverse pathologies These techniques allow real-time monitoring and generate a large amount of information, on the focus of the study, but on the biological environment [3]. Specific imaging of biomarkers allows earlier detection and characterization of a given disease, earlier and direct molecular assessment of treatment effects, and a more fundamental understanding of the disease process [4] Imaging modalities such as ultrasound (US), X-ray (Rx), magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission tomography (SPECT), and optical imaging (OI) allow the creation of in vivo images, providing information additional to the classic diagnosis, monitoring, and prognosis in oncological pathologies, and can be used to guide different medical procedures in situ [5–7]. Light scattering and autofluorescence are lower in the NIR, enabling higher signal-to-background ratios [8]

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