{"title":"In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer.","authors":"Min Zhang, Yue Xi, Hong Chen, Wangxi Hai, Biao Li","doi":"10.1155/2022/7456365","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Extracellular acidity is a marker of highly aggressive breast cancer (BC). pH-low insertion peptides (pHLIPs) target the acidic tumor microenvironment. This study evaluates the distribution and therapeutic efficacy of radioiodine-labeled pHLIP variant 3 (Var3) in a mouse model of BC.</p><p><strong>Methods: </strong>The binding of fluorescein isothiocyanate (FITC)- or radioiodine-125 (<sup>125</sup>I) labeled Var3-pHLIP to MDA-MB-231, 4T1, and SK-BR-3 BC cell lines under different pH values was evaluated in vitro. The distribution of <sup>125</sup>I-labeled Var3-pHLIP and wild-type- (WT-) pHLIP in tumor-bearing mice was analyzed in vivo using micro-SPECT/CT imaging. The therapeutic efficacy of radioiodine-131 (<sup>131</sup>I)-labeled Var3-pHLIP in MDA-MB-231 xenografts was evaluated by relative tumor volume measurement and immunohistochemical analysis.</p><p><strong>Results: </strong>The binding ability of FITC- or <sup>125</sup>I-labeled Var3-pHLIP to tumor cells increased with the decrease in pH. The tumor-to-background ratio of <sup>125</sup>I-Var3-pHLIP in BC xenografts showed the best imaging contrast at 24 h or 48 h postinjection. The uptake of <sup>125</sup>I-Var3-pHLIP in MDA-MB-231 xenografts at 2 h postinjection was significantly higher than that of <sup>125</sup>I-WT-pHLIP (3.76 ± 0.37 vs. 2.87 ± 0.60%ID/g, <i>p</i> = 0.046). The relative tumor volume in MDA-MB-231 xenografts was significantly lower in the <sup>131</sup>I-Var3-pHLIP-treated group than in the groups treated with Var3-pHLIP (<i>p</i> = 0.027), <sup>131</sup>I (<i>p</i> = 0.001), and saline (<i>p</i> < 0.001). The <sup>131</sup>I-Var 3-pHLIP group presented a lower expression of Ki67 and a higher expression of caspase 3.</p><p><strong>Conclusion: </strong>Radioiodine-labeled Var3-pHLIP effectively targeted BC cells in an acidic environment and inhibited the growth of MDA-MB-231 xenografts by ionizing radiation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"7456365"},"PeriodicalIF":4.6000,"publicationDate":"2022-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281440/pdf/","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2022/7456365","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 2
Abstract
Purpose: Extracellular acidity is a marker of highly aggressive breast cancer (BC). pH-low insertion peptides (pHLIPs) target the acidic tumor microenvironment. This study evaluates the distribution and therapeutic efficacy of radioiodine-labeled pHLIP variant 3 (Var3) in a mouse model of BC.
Methods: The binding of fluorescein isothiocyanate (FITC)- or radioiodine-125 (125I) labeled Var3-pHLIP to MDA-MB-231, 4T1, and SK-BR-3 BC cell lines under different pH values was evaluated in vitro. The distribution of 125I-labeled Var3-pHLIP and wild-type- (WT-) pHLIP in tumor-bearing mice was analyzed in vivo using micro-SPECT/CT imaging. The therapeutic efficacy of radioiodine-131 (131I)-labeled Var3-pHLIP in MDA-MB-231 xenografts was evaluated by relative tumor volume measurement and immunohistochemical analysis.
Results: The binding ability of FITC- or 125I-labeled Var3-pHLIP to tumor cells increased with the decrease in pH. The tumor-to-background ratio of 125I-Var3-pHLIP in BC xenografts showed the best imaging contrast at 24 h or 48 h postinjection. The uptake of 125I-Var3-pHLIP in MDA-MB-231 xenografts at 2 h postinjection was significantly higher than that of 125I-WT-pHLIP (3.76 ± 0.37 vs. 2.87 ± 0.60%ID/g, p = 0.046). The relative tumor volume in MDA-MB-231 xenografts was significantly lower in the 131I-Var3-pHLIP-treated group than in the groups treated with Var3-pHLIP (p = 0.027), 131I (p = 0.001), and saline (p < 0.001). The 131I-Var 3-pHLIP group presented a lower expression of Ki67 and a higher expression of caspase 3.
Conclusion: Radioiodine-labeled Var3-pHLIP effectively targeted BC cells in an acidic environment and inhibited the growth of MDA-MB-231 xenografts by ionizing radiation.
期刊介绍:
ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications.
The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.