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Development of (99m)Tc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental Study in Monitoring Drug Resistance of Non-Small-Cell Lung Cancer
SIMPLE SUMMARY: Non-small-cell lung cancer (NSCLC) represents approximately 80–85% of all lung cancers, and tumor resistance remains common and difficult to treat. Therefore, early detection of tumor resistance is of great significance for improving prognosis. Here, we developed a novel molecular im...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913320/ https://www.ncbi.nlm.nih.gov/pubmed/36765712 http://dx.doi.org/10.3390/cancers15030755 |
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author | Ye, Qianni Liu, Zhenfeng Zhang, Shuyi Wang, Guolin Wen, Guanghua Dong, Mengjie |
author_facet | Ye, Qianni Liu, Zhenfeng Zhang, Shuyi Wang, Guolin Wen, Guanghua Dong, Mengjie |
author_sort | Ye, Qianni |
collection | PubMed |
description | SIMPLE SUMMARY: Non-small-cell lung cancer (NSCLC) represents approximately 80–85% of all lung cancers, and tumor resistance remains common and difficult to treat. Therefore, early detection of tumor resistance is of great significance for improving prognosis. Here, we developed a novel molecular imaging agent that could be used for imaging drug-resistant NSCLC, providing a noninvasive method for dynamically observing whether tumor resistance occurs during treatment. ABSTRACT: Background: N-cadherin is considered a characteristic protein of EMT and has been found to be closely related to tumor resistance. In this study, a novel molecular imaging probe, (99m)Tc-HYNIC-ADH-1, was developed, and its diagnostic value in monitoring drug resistance in NSCLC was preliminarily investigated. Methods: ADH-1 was labeled indirectly with (99m)Tc. Radiochemical purity and stability, partition coefficients and pharmacokinetics were evaluated. Additionally, the fluorescent probe of ADH-1 was synthesized to study tumor uptake in cells level and in vivo. Biodistribution analysis and small animal SPECT/CT were performed in PC9GR and PC9 tumor-bearing mice. Results: (99m)Tc-HYNIC-ADH-1 was highly stable (radiochemical purity ≥ 98% in PBS and serum after 24 h). A cell binding study and fluorescence imaging showed that the uptake was significantly higher in PC9GR cells (gefitinib-resistant) than in PC9 cells (nonresistant) (p < 0.05). Biodistribution analysis showed rapid blood clearance and significant uptake in the kidney and resistant tumor. Small animal SPECT/CT studies showed that uptake in PC9GR tumors (T/NT = 7.73 ± 0.54) was significantly higher than that in PC9 tumors (T/NT = 3.66 ± 0.78) at 1 h (p = 0.002). Conclusions: The (99m)Tc-HYNIC-ADH-1 molecular probe has a short synthesis time, high labeling rate, high radiochemical purity and good stability, does not require purification, is characterized by rapid blood clearance and is mainly excreted through the urinary system. (99m)Tc-HYNIC-ADH-1 is considered a promising probe for monitoring drug resistance in NSCLC. |
format | Online Article Text |
id | pubmed-9913320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99133202023-02-11 Development of (99m)Tc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental Study in Monitoring Drug Resistance of Non-Small-Cell Lung Cancer Ye, Qianni Liu, Zhenfeng Zhang, Shuyi Wang, Guolin Wen, Guanghua Dong, Mengjie Cancers (Basel) Article SIMPLE SUMMARY: Non-small-cell lung cancer (NSCLC) represents approximately 80–85% of all lung cancers, and tumor resistance remains common and difficult to treat. Therefore, early detection of tumor resistance is of great significance for improving prognosis. Here, we developed a novel molecular imaging agent that could be used for imaging drug-resistant NSCLC, providing a noninvasive method for dynamically observing whether tumor resistance occurs during treatment. ABSTRACT: Background: N-cadherin is considered a characteristic protein of EMT and has been found to be closely related to tumor resistance. In this study, a novel molecular imaging probe, (99m)Tc-HYNIC-ADH-1, was developed, and its diagnostic value in monitoring drug resistance in NSCLC was preliminarily investigated. Methods: ADH-1 was labeled indirectly with (99m)Tc. Radiochemical purity and stability, partition coefficients and pharmacokinetics were evaluated. Additionally, the fluorescent probe of ADH-1 was synthesized to study tumor uptake in cells level and in vivo. Biodistribution analysis and small animal SPECT/CT were performed in PC9GR and PC9 tumor-bearing mice. Results: (99m)Tc-HYNIC-ADH-1 was highly stable (radiochemical purity ≥ 98% in PBS and serum after 24 h). A cell binding study and fluorescence imaging showed that the uptake was significantly higher in PC9GR cells (gefitinib-resistant) than in PC9 cells (nonresistant) (p < 0.05). Biodistribution analysis showed rapid blood clearance and significant uptake in the kidney and resistant tumor. Small animal SPECT/CT studies showed that uptake in PC9GR tumors (T/NT = 7.73 ± 0.54) was significantly higher than that in PC9 tumors (T/NT = 3.66 ± 0.78) at 1 h (p = 0.002). Conclusions: The (99m)Tc-HYNIC-ADH-1 molecular probe has a short synthesis time, high labeling rate, high radiochemical purity and good stability, does not require purification, is characterized by rapid blood clearance and is mainly excreted through the urinary system. (99m)Tc-HYNIC-ADH-1 is considered a promising probe for monitoring drug resistance in NSCLC. MDPI 2023-01-26 /pmc/articles/PMC9913320/ /pubmed/36765712 http://dx.doi.org/10.3390/cancers15030755 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ye, Qianni Liu, Zhenfeng Zhang, Shuyi Wang, Guolin Wen, Guanghua Dong, Mengjie Development of (99m)Tc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental Study in Monitoring Drug Resistance of Non-Small-Cell Lung Cancer |
title | Development of (99m)Tc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental Study in Monitoring Drug Resistance of Non-Small-Cell Lung Cancer |
title_full | Development of (99m)Tc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental Study in Monitoring Drug Resistance of Non-Small-Cell Lung Cancer |
title_fullStr | Development of (99m)Tc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental Study in Monitoring Drug Resistance of Non-Small-Cell Lung Cancer |
title_full_unstemmed | Development of (99m)Tc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental Study in Monitoring Drug Resistance of Non-Small-Cell Lung Cancer |
title_short | Development of (99m)Tc-Hynic-Adh-1 Molecular Probe Specifically Targeting N-Cadherin and Its Preliminary Experimental Study in Monitoring Drug Resistance of Non-Small-Cell Lung Cancer |
title_sort | development of (99m)tc-hynic-adh-1 molecular probe specifically targeting n-cadherin and its preliminary experimental study in monitoring drug resistance of non-small-cell lung cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913320/ https://www.ncbi.nlm.nih.gov/pubmed/36765712 http://dx.doi.org/10.3390/cancers15030755 |
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