Preparation and SPECT/CT Imaging of 177Lu-Labeled Peptide Nucleic Acid (PNA) Targeting CITED1: Therapeutic Evaluation in Tumor-Bearing Nude Mice

Autor: Lei Zhang, Ying Wang, Chengming Lei, Hua Pang, Yiyi Cao, Zhengjie Wang, Wenbo Li, Jia Li
Rok vydání: 2020
Předmět:
Zdroj: OncoTargets and Therapy. 13:487-496
ISSN: 1178-6930
DOI: 10.2147/ott.s238098
Popis: Purpose The expression of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal 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 177Lu-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 177Lu-DOTA-anti-CITED1-PNA (177Lu-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 177Lu-asPNA was evaluated by TLC, and the radioactivity count was measured by a γ counter to calculate its uptake capacity in K1 cells. To analyze the distribution of 177Lu-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±0.15% at 1 hr and specific activity of 8.7±0.53 MBq/μg. The uptake rate in the 177Lu-asPNA group was much higher than that in the 177Lu-DOTA-nonsense-PNA (177Lu-nonsense-PNA) and 177Lu-DOTA groups (P
Databáze: OpenAIRE
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