Preparation and SPECT/CT Imaging of 177Lu-Labeled Peptide…

Preparation and SPECT/CT Imaging of 177Lu-Labeled Peptide Nucleic Acid (PNA) Targeting CITED1: Therapeutic Evaluation in Tumor-Bearing Nude Mice Jia Li, Lei Zhang, Wenbo Li, Chengming Lei, Yiyi Cao, Ying Wang, Zhengjie Wang, Hua Pang Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Hua Pang; Zhengjie WangDepartment of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, People’s Republic of ChinaTel +8615923039337; +8618581493311Email phua1973@163.com; bkzg1234@163.comPurpose: 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< 0.05). The biological distribution showed that the tumor/muscle ratio was at its highest at 24 h (4.98± 0.34) post-inoculation, with SPECT/CT imaging showing clear tumor development. By measuring tumor volume of tumor-bearing nude mice, the 177Lu-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 177Lu-asPNA group was significantly different from those in the DOTA-anti-CITED1-PNA (asPNA) and saline groups (P = 0.002, log-rank test).Conclusion: 177Lu-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

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