Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 56, Issue 4, Pages 616-621Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.114.149484
Keywords
DNA aptamer; tenascin-C; PET
Funding
- intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), National Basic Research Program of China [2014CB744503, 2013CB733802, 2015CB931800, 2015CB931803]
- National Natural Science Foundation of China [81371596, 81130028, 31210103913]
- Key Grant Project of Heilongjiang Province [GA12C302]
- PhD Programs Foundation of Ministry of Education of China [201123071100203]
- Key Laboratory of Molecular Imaging Foundation (College of Heilongjiang Province)
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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 F-18 and Cu-64. 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.
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