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Journal of Nuclear Medicine

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Application and Evaluation of [99mTc]-Labeled Peptide Nucleic Acid Targeting MicroRNA-155 in Breast Cancer Imaging

Yaqun Jiang, Yongkang Gai, Yongxue Zhang and Xiaoli Lan
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 1092;
Yaqun Jiang
1Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China
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Yongkang Gai
1Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China
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Yongxue Zhang
1Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China
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Xiaoli Lan
1Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China
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Abstract

1092

Objectives: It has been reported that dysregulation of microRNA-155 (miRNA-155, miR-155) expression and function is associated with tumorigenesis, growth, tumor subtypes, invasion, and poor survival rates. Peptide nucleic acid (PNA), an artificially synthesized nucleic acid mimic, has been widely applied for molecular diagnosis. In this study, a PNA sequence which undergoes complementary binding to miR-155 was labeled with 99mTc to evaluate whether the tracer could visualize the expression of miR-155 in breast cancer. Methods: Both antisense PNA (anti-PNA, fully complementary bound to human mature miR-155, referred to as “anti-PNA-155”) and mismatched PNA (referred to as “mis-PNA”) single strands containing 23-mer were chemically synthesized. For labeling, a short peptide consisting of 4 amino acids (Gly-(D)-Ala-Gly-Gly) which can form a N4 structure was applied to chelate with 99mTc by ligand exchange. The radiochemical yield, purity and stability of 99mTc labeled probes were determined by analytical high performance liquid chromatography (HPLC). Cellular assays were performed in vitro. Single photon emission computed tomography (SPECT) and biodistribution study were carried out in MCF-7 and MDA-MB-231 xenografts. Results: Anti-PNA-155 and mis-PNA were successfully labeled with 99mTc with high radiochemical yields and purity and good stability. The relative expression of miR-155 in MCF-7 cells and tumors was higher than in MDA-MB-231 cells and tumors. Static SPECT scan showed that radioactivity mainly accumulated in kidney and liver. On SPECT images, MCF-7 tumors, but not MDA-MB-231 tumors, were clearly visualized after [99mTc]anti-PNA-155 injection. MCF-7 tumors were less visible when co-injected with 100-fold excess of anti-PNA-155 or injected with [99mTc]mis-PNA, which suggested specific binding. Biodistribution studies results were consistent with SPECT imaging.

Conclusions: We successfully demonstrated that [99mTc]anti-PNA-155 could visualize miR-155 expression in vivo, suggesting it may be a promising probe applied in breast cancer. Acknowledgement: This work was supported by the National Natural Science Foundation of China (No. 81630049, 81771863 and 81801738).

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Journal of Nuclear Medicine
Vol. 61, Issue supplement 1
May 1, 2020
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Application and Evaluation of [99mTc]-Labeled Peptide Nucleic Acid Targeting MicroRNA-155 in Breast Cancer Imaging
Yaqun Jiang, Yongkang Gai, Yongxue Zhang, Xiaoli Lan
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 1092;

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Application and Evaluation of [99mTc]-Labeled Peptide Nucleic Acid Targeting MicroRNA-155 in Breast Cancer Imaging
Yaqun Jiang, Yongkang Gai, Yongxue Zhang, Xiaoli Lan
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 1092;
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