Preparation and SPECT/CT Imaging of [.sup.177]Lu-Labeled Peptide Nucleic Acid

Purpose: The expression of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxyterminal domain 1 (CITED1) is upregulated in papillary thyroid carcinoma (PTC) and mediates cell proliferation and migration. To facilitate early diagnosis and monitoring of recurrent or metastatic PTC, we design...

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Published inOncoTargets and therapy Vol. 13; p. 487
Main Authors Pang, Hua, Lei, Chengming, Li, Wenbo, Li, Jia, Cao, Yiyi, Zhang, Lei, Wang, Ying, Wang, Zhengjie
Format Journal Article
LanguageEnglish
Published Dove Medical Press Limited 01.01.2020
Subjects
Cancer
Cancer metastasis
Carcinoma
CAT scans
Chromatography
Diagnostic imaging
Health aspects
High performance liquid chromatography
Liquid chromatography
Messenger RNA
Nucleic acids
Peptides
RNA
Single photon emission computed tomography
Thyroid diseases
Tomography
Tumors
China
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Summary:Purpose: The expression of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxyterminal domain 1 (CITED1) is upregulated in papillary thyroid carcinoma (PTC) and mediates cell proliferation and migration. To facilitate early diagnosis and monitoring of recurrent or metastatic PTC, we designed [.sup.177]Lu-labeled antisense peptide nucleic acid (PNA) targeting CITED1 mRNA to evaluate the therapeutic potential, while analyzing its distribution in nude mice and the characteristics withsingle-photon emission-computed tomography/computed tomography (SPECT/CT) imaging. Materials and Methods: [.sup.177]Lu-DOTA-anti-CITED1-PNA ([.sup.177]Lu-asPNA) was obtained by indirect labeling. High-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) were used to determine the labeling rate and radiochemical purity. The stability of [.sup.177]Lu-asPNA was evaluated by TLC, and the radioactivity count was measured by a [gamma] counter to calculate its uptake capacity in K1 cells. To analyze the distribution of [.sup.177]Lu-asPNA in body tissues and organs of nude mice, static single-photon emission-computed tomography (SPECT) imaging and SPECT/CT image fusion were performed. Then, the therapeutic effects of probes were explored by tumor growth curves and survival analysis. Results: Our probe showed a radiochemical purity of 96.5[+ or -]0.15% at 1 hr and specific activity of 8.7[+ or -]0.53 MBq/[micro]g. The uptake rate in the [.sup.177]Lu-asPNA group was much higher than that in the [.sup.177]Lu-DOTA-nonsense-PNA ([.sup.177]Lu-nonsense-PNA) and [.sup.177]Lu-DOTA groups (P<0.05). The biological distribution showed that the tumor/muscle ratio was at its highest at 24 h (4.98[+ or -]0.34) post-inoculation, with SPECT/CT imaging showing clear tumor development. By measuring tumor volume of tumor-bearing nude mice, the [.sup.177]Lu-asPNA group showed a significant difference in tumor size 9 days after injection (P < 0.05). Kaplan-Meier survival curves showed that the overall survival rate in the [.sup.177]Lu-asPNA group was significantly different from those in the DOTA-anti-CITED1-PNA (asPNA) and saline groups (P = 0.002, log-rank test). Conclusion: [.sup.177]Lu-asPNA was developed successfully, showing a high labeling rate and good stability. SPECT/CT imaging demonstrated tumor growth in nude mice, which was effectively inhibited by our probe, thus prolonging survival. Keywords: antisense therapy, SPECT/CT imaging, papillary thyroid carcinoma, diagnosis and treatment integration
ISSN:1178-6930
1178-6930