Lan Wang, Shengnan Ren, Jingjing Lou, Shuai Xue, Pan Zhou, Xiaobei Zheng, Fengling Shan, Xiao Li, Yangchun Chen, Xingdang Liu
{"title":"基于e - urea的PSMA成像可通过靶向CD31评估肿瘤新生血管","authors":"Lan Wang, Shengnan Ren, Jingjing Lou, Shuai Xue, Pan Zhou, Xiaobei Zheng, Fengling Shan, Xiao Li, Yangchun Chen, Xingdang Liu","doi":"10.1021/acs.molpharmaceut.4c01252","DOIUrl":null,"url":null,"abstract":"<p><p>To reveal the natural correlation between prostate-specific membrane antigen (PSMA) imaging and tumor neovascularization in prostate cancer and further explore E-urea-K-based PSMA-targeted (EK-PSMA) imaging as a potential indicator of tumor neovascularization, the 22Rv1 mouse models were established and underwent <sup>99m</sup>Tc-HYNIC-ALUG SPECT/CT. Pearson correlation analysis was applied to assess the relationship between tumor tracer uptake and tumor characteristics, including size, glucose metabolism, and cell phenotypes (e.g., Ki-67, VEGF, CD31, and PSMA). Then, molecular docking further identified the key factors of EK-PSMA imaging, specifically related to tumor neovascularization. Finally, animal models with positive and negative PSMA expression (22Rv1, LNCaP, U87, SAOS-2, A549, and ACHN) were subjected to antibody-targeted blockade to verify the role of these key factors in EK-PSMA imaging. The Pearson's <i>r</i> values of tracer uptake correlated with CD31 and tumor size were 0.82 and 0.99, respectively (<i>P</i> < 0.05), and the correlations of tracer uptake with SUV<sub>max</sub>, SUV<sub>mean</sub>, Ki-67, VEGF, and PSMA expressions were 0.47, 0.20, 0.69, -0.65, and 0.20, respectively (all <i>P</i> > 0.05). Molecular docking confirmed the affinity of E-urea-K to PSMA (two sites, binding scores, -5.4 kcal/mol and -6.0 kcal/mol) and CD31 (one site, binding score, -5.1 kcal/mol). The blockade of the CD31 antibody partially reduced the <sup>99m</sup>Tc-HYNIC-ALUG uptake in five other types of tumors (paired <i>t</i> test, <i>P</i> = 0.0478). The Pearson's <i>r</i> value of CD31 staining and tracer uptake prior to the antibody blockade was 0.84 (<i>P</i> < 0.05). Additionally, when removing the PSMA-positive models (22Rv1 and LNCaP), the Pearson's <i>r</i> value of CD31 staining and tracer uptake prior to the antibody blockade was 0.99 (<i>P</i> < 0.05). Thus, CD31 was found to be a mutual target of EK-PSMA imaging; therefore, EK-PSMA imaging provides a viable assessment option for tumor neovascularization, especially for PSMA-negative tumors.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"2029-2039"},"PeriodicalIF":4.5000,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"E-Urea-K-Based PSMA Imaging Served as an Alternative in Assessing Tumor Neovascularization via Targeting CD31.\",\"authors\":\"Lan Wang, Shengnan Ren, Jingjing Lou, Shuai Xue, Pan Zhou, Xiaobei Zheng, Fengling Shan, Xiao Li, Yangchun Chen, Xingdang Liu\",\"doi\":\"10.1021/acs.molpharmaceut.4c01252\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>To reveal the natural correlation between prostate-specific membrane antigen (PSMA) imaging and tumor neovascularization in prostate cancer and further explore E-urea-K-based PSMA-targeted (EK-PSMA) imaging as a potential indicator of tumor neovascularization, the 22Rv1 mouse models were established and underwent <sup>99m</sup>Tc-HYNIC-ALUG SPECT/CT. Pearson correlation analysis was applied to assess the relationship between tumor tracer uptake and tumor characteristics, including size, glucose metabolism, and cell phenotypes (e.g., Ki-67, VEGF, CD31, and PSMA). Then, molecular docking further identified the key factors of EK-PSMA imaging, specifically related to tumor neovascularization. Finally, animal models with positive and negative PSMA expression (22Rv1, LNCaP, U87, SAOS-2, A549, and ACHN) were subjected to antibody-targeted blockade to verify the role of these key factors in EK-PSMA imaging. The Pearson's <i>r</i> values of tracer uptake correlated with CD31 and tumor size were 0.82 and 0.99, respectively (<i>P</i> < 0.05), and the correlations of tracer uptake with SUV<sub>max</sub>, SUV<sub>mean</sub>, Ki-67, VEGF, and PSMA expressions were 0.47, 0.20, 0.69, -0.65, and 0.20, respectively (all <i>P</i> > 0.05). Molecular docking confirmed the affinity of E-urea-K to PSMA (two sites, binding scores, -5.4 kcal/mol and -6.0 kcal/mol) and CD31 (one site, binding score, -5.1 kcal/mol). The blockade of the CD31 antibody partially reduced the <sup>99m</sup>Tc-HYNIC-ALUG uptake in five other types of tumors (paired <i>t</i> test, <i>P</i> = 0.0478). The Pearson's <i>r</i> value of CD31 staining and tracer uptake prior to the antibody blockade was 0.84 (<i>P</i> < 0.05). Additionally, when removing the PSMA-positive models (22Rv1 and LNCaP), the Pearson's <i>r</i> value of CD31 staining and tracer uptake prior to the antibody blockade was 0.99 (<i>P</i> < 0.05). Thus, CD31 was found to be a mutual target of EK-PSMA imaging; therefore, EK-PSMA imaging provides a viable assessment option for tumor neovascularization, especially for PSMA-negative tumors.</p>\",\"PeriodicalId\":52,\"journal\":{\"name\":\"Molecular Pharmaceutics\",\"volume\":\" \",\"pages\":\"2029-2039\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-04-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.molpharmaceut.4c01252\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.molpharmaceut.4c01252","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
E-Urea-K-Based PSMA Imaging Served as an Alternative in Assessing Tumor Neovascularization via Targeting CD31.
To reveal the natural correlation between prostate-specific membrane antigen (PSMA) imaging and tumor neovascularization in prostate cancer and further explore E-urea-K-based PSMA-targeted (EK-PSMA) imaging as a potential indicator of tumor neovascularization, the 22Rv1 mouse models were established and underwent 99mTc-HYNIC-ALUG SPECT/CT. Pearson correlation analysis was applied to assess the relationship between tumor tracer uptake and tumor characteristics, including size, glucose metabolism, and cell phenotypes (e.g., Ki-67, VEGF, CD31, and PSMA). Then, molecular docking further identified the key factors of EK-PSMA imaging, specifically related to tumor neovascularization. Finally, animal models with positive and negative PSMA expression (22Rv1, LNCaP, U87, SAOS-2, A549, and ACHN) were subjected to antibody-targeted blockade to verify the role of these key factors in EK-PSMA imaging. The Pearson's r values of tracer uptake correlated with CD31 and tumor size were 0.82 and 0.99, respectively (P < 0.05), and the correlations of tracer uptake with SUVmax, SUVmean, Ki-67, VEGF, and PSMA expressions were 0.47, 0.20, 0.69, -0.65, and 0.20, respectively (all P > 0.05). Molecular docking confirmed the affinity of E-urea-K to PSMA (two sites, binding scores, -5.4 kcal/mol and -6.0 kcal/mol) and CD31 (one site, binding score, -5.1 kcal/mol). The blockade of the CD31 antibody partially reduced the 99mTc-HYNIC-ALUG uptake in five other types of tumors (paired t test, P = 0.0478). The Pearson's r value of CD31 staining and tracer uptake prior to the antibody blockade was 0.84 (P < 0.05). Additionally, when removing the PSMA-positive models (22Rv1 and LNCaP), the Pearson's r value of CD31 staining and tracer uptake prior to the antibody blockade was 0.99 (P < 0.05). Thus, CD31 was found to be a mutual target of EK-PSMA imaging; therefore, EK-PSMA imaging provides a viable assessment option for tumor neovascularization, especially for PSMA-negative tumors.
期刊介绍：
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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