PET imaging of tenascin-C with a radiolabeled single-stranded DNA aptamer.

Abstract

UNLABELLED:

Tenascin-C is an extracellular matrix glycoprotein that is expressed by injured tissues and by various cancers. Recent publications showed that tenascin-C expression by cancer lesions predicts tumor growth, metastasis, and angiogenesis, suggesting tenascin-C as a potential therapeutic target. Currently there is no noninvasive method to determine tumoral tenascin-C expression in vivo. To address the need for an agent to image and quantify tenascin-C, we report the development of a radioactive PET tracer based on a tenascin-C-specific single-stranded DNA aptamer (tenascin-C aptamer).

METHODS:

Tenascin-C aptamer was radiolabeled with (18)F and (64)Cu. PET imaging studies for the evaluation of tumor uptake and pharmacokinetics of tenascin-C aptamer were performed in comparison to a nonspecific scrambled aptamer (Sc aptamer).

RESULTS:

The labeled tenascin-C aptamer provided clear visualization of tenascin-C-positive but not tenascin-C-negative tumors. The uptake of tenascin-C aptamer was significantly higher than that of Sc aptamer in tenascin-C-positive tumors. The labeled tenascin-C aptamer had fast clearance from the blood and other nonspecific organs through the kidneys, resulting in high tumor contrast.

CONCLUSION:

Our data suggest that suitably labeled tenascin-C aptamer can be used as a PET tracer to image tumor expression of tenascin-C with a high tumor-to-background ratio and might provide insightful and personalized medical data that will help determine appropriate treatment and monitoring.

• Authors: Orit Jacobson, Xuefeng Yan, Gang Niu, Ido D Weiss, Ying Ma, Lawrence P Szajek, Baozhong Shen, Dale O Kiesewetter, Xiaoyuan Chen
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 56 Issue 4 Pg. 616-21 (Apr 2015) ISSN: 1535-5667 [Electronic] United States
• PMID: 25698784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

• Aptamers, Nucleotide
• Copper Radioisotopes
• DNA, Single-Stranded
• Fluorine Radioisotopes
• Nucleotides
• Radioactive Tracers
• Radiopharmaceuticals
• Tenascin

Topics

• Animals
• Aptamers, Nucleotide (chemistry)
• Cell Line, Tumor
• Copper Radioisotopes (chemistry)
• DNA, Single-Stranded (chemistry)
• Diagnostic Imaging
• Female
• Fluorine Radioisotopes (chemistry)
• Humans
• Mice
• Mice, Nude
• Microscopy, Fluorescence
• Neoplasm Transplantation
• Nucleic Acid Conformation
• Nucleotides (chemistry)
• Positron-Emission Tomography (methods)
• Radioactive Tracers
• Radiopharmaceuticals
• Tenascin (chemistry)