Tae-Hun Hahm, Dalton R Brown, Caitlin M Tressler, Thao Tran, Alice Ly, Arvind P Pathak, Michael T McMahon, Kristine Glunde
{"title":"三阴性乳腺癌小鼠模型中阿司匹林代谢物的定量MALDI成像。","authors":"Tae-Hun Hahm, Dalton R Brown, Caitlin M Tressler, Thao Tran, Alice Ly, Arvind P Pathak, Michael T McMahon, Kristine Glunde","doi":"10.7150/thno.116819","DOIUrl":null,"url":null,"abstract":"<p><p><b>Rationale:</b> The non-steroidal anti-inflammatory drug aspirin is currently being developed as activatable contrast agent for chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI), for detection of its CEST MRI active metabolite salicylic acid (SA). This study refines and develops quantitative matrix-assisted laser desorption/ionization (QMALDI) imaging to investigate the distribution of aspirin metabolites including SA in triple-negative breast cancer (TNBC) models in mice. <b>Method:</b> In this study, we established QMALDI imaging with norharmane (nH) matrix and assisted by the addition of 5 mM peracetic acid (PAA) for optimized SA detection. Deuterated D<sub>6</sub>-SA was added as an internal standard to quantify SA detection. PAA was applied via spraying to improve matrix uniformity and reduce crystal size by forming hydrogen bonds with the nH matrix. Ultraviolet (UV) irradiation during MALDI imaging activated PAA, generating reactive radicals that facilitated the breakdown of nH matrix compounds, thereby reducing matrix-related noise. <b>Results:</b> QMALDI imaging with 5 mM PAA-doped nH matrix and D<sub>6</sub>-SA as internal standard revealed SA accumulation of 141.9 ± 22.6 pmol/mm² in the liver, 129.5 ± 7.8 pmol/mm² in the kidney, and 50.4 ± 3.0 pmol/mm² in TNBC tumors following intravenous injection of aspirin in mice. Precise spatial alignment, integration, and quantification of MALDI imaging, histology, and immunofluorescence images from CD31 staining for blood vessels allowed us to accurately evaluate the spatial distribution of SA in tissue regions enriched with blood vessels and in specific anatomical regions. This spatial data analysis revealed high SA accumulation in the kidney medulla, viable tumor rim containing CD31-stained blood vessels, and throughout the liver. <b>Conclusion:</b> This newly developed QMALDI imaging approach for detecting aspirin metabolites demonstrated high SA accumulation in the kidney medulla and tumor rim containing blood vessels within viable tumor regions following systemic aspirin injection in mice, consistent with our previous study using aspirin-generated SA as activated contrast agent for CEST MRI. This approach enhances the spatial and tissue structural accuracy of quantitative analysis, reinforcing the potential of QMALDI imaging for investigating contrast agents, drug distributions, and metabolism in various tissues.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9359-9374"},"PeriodicalIF":13.3000,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486018/pdf/","citationCount":"0","resultStr":"{\"title\":\"Quantitative MALDI imaging of aspirin metabolites in mouse models of triple-negative breast cancer.\",\"authors\":\"Tae-Hun Hahm, Dalton R Brown, Caitlin M Tressler, Thao Tran, Alice Ly, Arvind P Pathak, Michael T McMahon, Kristine Glunde\",\"doi\":\"10.7150/thno.116819\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Rationale:</b> The non-steroidal anti-inflammatory drug aspirin is currently being developed as activatable contrast agent for chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI), for detection of its CEST MRI active metabolite salicylic acid (SA). This study refines and develops quantitative matrix-assisted laser desorption/ionization (QMALDI) imaging to investigate the distribution of aspirin metabolites including SA in triple-negative breast cancer (TNBC) models in mice. <b>Method:</b> In this study, we established QMALDI imaging with norharmane (nH) matrix and assisted by the addition of 5 mM peracetic acid (PAA) for optimized SA detection. Deuterated D<sub>6</sub>-SA was added as an internal standard to quantify SA detection. PAA was applied via spraying to improve matrix uniformity and reduce crystal size by forming hydrogen bonds with the nH matrix. Ultraviolet (UV) irradiation during MALDI imaging activated PAA, generating reactive radicals that facilitated the breakdown of nH matrix compounds, thereby reducing matrix-related noise. <b>Results:</b> QMALDI imaging with 5 mM PAA-doped nH matrix and D<sub>6</sub>-SA as internal standard revealed SA accumulation of 141.9 ± 22.6 pmol/mm² in the liver, 129.5 ± 7.8 pmol/mm² in the kidney, and 50.4 ± 3.0 pmol/mm² in TNBC tumors following intravenous injection of aspirin in mice. Precise spatial alignment, integration, and quantification of MALDI imaging, histology, and immunofluorescence images from CD31 staining for blood vessels allowed us to accurately evaluate the spatial distribution of SA in tissue regions enriched with blood vessels and in specific anatomical regions. This spatial data analysis revealed high SA accumulation in the kidney medulla, viable tumor rim containing CD31-stained blood vessels, and throughout the liver. <b>Conclusion:</b> This newly developed QMALDI imaging approach for detecting aspirin metabolites demonstrated high SA accumulation in the kidney medulla and tumor rim containing blood vessels within viable tumor regions following systemic aspirin injection in mice, consistent with our previous study using aspirin-generated SA as activated contrast agent for CEST MRI. This approach enhances the spatial and tissue structural accuracy of quantitative analysis, reinforcing the potential of QMALDI imaging for investigating contrast agents, drug distributions, and metabolism in various tissues.</p>\",\"PeriodicalId\":22932,\"journal\":{\"name\":\"Theranostics\",\"volume\":\"15 18\",\"pages\":\"9359-9374\"},\"PeriodicalIF\":13.3000,\"publicationDate\":\"2025-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486018/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Theranostics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7150/thno.116819\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.116819","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Quantitative MALDI imaging of aspirin metabolites in mouse models of triple-negative breast cancer.
Rationale: The non-steroidal anti-inflammatory drug aspirin is currently being developed as activatable contrast agent for chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI), for detection of its CEST MRI active metabolite salicylic acid (SA). This study refines and develops quantitative matrix-assisted laser desorption/ionization (QMALDI) imaging to investigate the distribution of aspirin metabolites including SA in triple-negative breast cancer (TNBC) models in mice. Method: In this study, we established QMALDI imaging with norharmane (nH) matrix and assisted by the addition of 5 mM peracetic acid (PAA) for optimized SA detection. Deuterated D6-SA was added as an internal standard to quantify SA detection. PAA was applied via spraying to improve matrix uniformity and reduce crystal size by forming hydrogen bonds with the nH matrix. Ultraviolet (UV) irradiation during MALDI imaging activated PAA, generating reactive radicals that facilitated the breakdown of nH matrix compounds, thereby reducing matrix-related noise. Results: QMALDI imaging with 5 mM PAA-doped nH matrix and D6-SA as internal standard revealed SA accumulation of 141.9 ± 22.6 pmol/mm² in the liver, 129.5 ± 7.8 pmol/mm² in the kidney, and 50.4 ± 3.0 pmol/mm² in TNBC tumors following intravenous injection of aspirin in mice. Precise spatial alignment, integration, and quantification of MALDI imaging, histology, and immunofluorescence images from CD31 staining for blood vessels allowed us to accurately evaluate the spatial distribution of SA in tissue regions enriched with blood vessels and in specific anatomical regions. This spatial data analysis revealed high SA accumulation in the kidney medulla, viable tumor rim containing CD31-stained blood vessels, and throughout the liver. Conclusion: This newly developed QMALDI imaging approach for detecting aspirin metabolites demonstrated high SA accumulation in the kidney medulla and tumor rim containing blood vessels within viable tumor regions following systemic aspirin injection in mice, consistent with our previous study using aspirin-generated SA as activated contrast agent for CEST MRI. This approach enhances the spatial and tissue structural accuracy of quantitative analysis, reinforcing the potential of QMALDI imaging for investigating contrast agents, drug distributions, and metabolism in various tissues.
期刊介绍:
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.