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

Abstract

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 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: 177 Lu-DOTA-anti-CITED1-PNA (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 177 Lu-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 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±0.15% at 1 hr and specific activity of 8.7±0.53 MBq/μg. The uptake rate in the 177 Lu-asPNA group was much higher than that in the 177 Lu-DOTA-nonsense-PNA (177 Lu-nonsense-PNA) and 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±0.34) post-inoculation, with SPECT/CT imaging showing clear tumor development. By measuring tumor volume of tumor-bearing nude mice, the 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 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: 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.

Effect of silencing CITED1 gene to regulate PI3K/AKT pathway on the biological function of PTC cells and its mechanism

“…The PI3K/AKT pathway, which promotes the transcription of proto-oncogenes, is one of the most critical pathways triggering the occurrence and development of PTC, and inhibition of the pathway has become a target for PTC treatment; however, the mechanism of PI3K/ AKT pathway regulation in PTC remains unclear (3). The CITED1 gene is located on chromosome Xq13.1 and encodes the 27 kD nuclear protein CITED1; as a transcriptional activator, the CITED1 protein can induce transcription and translation of protein kinase, thus promoting carcinoma metastasis (4). Recent studies have revealed that CITED1 is elevated in PTC tissues and can promote PTC progression, but the effects and molecular mechanisms of CITED1 on the biological behavior of PTC cells remain unclear (6).…”

Radiometal-Labeled Chitosan Microspheres as Transarterial Radioembolization Agents against Hepatocellular Carcinoma

“…Compared to 90 Y, imaging the distribution of 177 Lu in the living body is more straightforward. We can easily track 177 Lu-labeled microspheres and determine the dosimetry with noninvasive single photon emission computed tomography (SPECT) imaging [ 18 , 19 ]. To our knowledge, to date, no studies have been reported on the application of 177 Lu-labeled drugs in radioembolization for the treatment of hepatoma.…”

Site-Specific Radioiodination of Oligonucleotides with a Phenolic Element in a Programmable Approach

“…Radiolabeling of oligonucleotides facilitates the determination of pharmacokinetics and biodistribution of nucleic acid therapeutics by positron emission tomography (PET) and single-photon emission computed tomography (SPECT) [ 14 , 15 , 16 ], which will be beneficial for patients under the therapies directed by molecular imaging. Furthermore, radiolabeling aptamers are potential imaging probes for clinical diagnosis to visualize the in vivo biological process on the molecular level [ 17 , 18 , 19 ].…”