Quantitative MALDI imaging of aspirin metabolites in mouse models of triple-negative breast cancer.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-22 eCollection Date: 2025-01-01 DOI:10.7150/thno.116819
Tae-Hun Hahm, Dalton R Brown, Caitlin M Tressler, Thao Tran, Alice Ly, Arvind P Pathak, Michael T McMahon, Kristine Glunde
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引用次数: 0

Abstract

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.

三阴性乳腺癌小鼠模型中阿司匹林代谢物的定量MALDI成像。
理由:非甾体抗炎药阿司匹林目前正被开发为化学交换饱和转移(CEST)磁共振成像(MRI)的可活化造影剂,用于检测其CEST MRI活性代谢物水杨酸(SA)。本研究改进并发展了定量基质辅助激光解吸/电离(QMALDI)成像技术,以研究包括SA在内的阿司匹林代谢物在小鼠三阴性乳腺癌(TNBC)模型中的分布。方法:本研究以诺哈曼(nH)为基质,添加5 mM过氧乙酸(PAA)辅助,建立QMALDI成像,优化SA检测。加入氘化D6-SA作为内标,定量检测SA。采用喷淋方式加入PAA,通过与nH基体形成氢键来改善基体均匀性,减小晶粒尺寸。MALDI成像过程中的紫外线(UV)照射激活了PAA,产生了活性自由基,促进了nH基质化合物的分解,从而减少了基质相关的噪声。结果:以5 mM paa掺杂的nH基质和D6-SA为内标的QMALDI显像显示,静脉注射阿司匹林后小鼠TNBC肿瘤内SA积累量为141.9±22.6 pmol/ mM²,肾脏为129.5±7.8 pmol/ mM²,TNBC肿瘤内SA积累量为50.4±3.0 pmol/ mM²。对MALDI成像、组织学和CD31血管染色的免疫荧光图像进行精确的空间比对、整合和量化,使我们能够准确评估SA在富含血管的组织区域和特定解剖区域的空间分布。该空间数据分析显示,高SA积聚在肾髓质、含有cd31染色血管的活肿瘤边缘和整个肝脏。结论:这种新开发的用于检测阿司匹林代谢物的QMALDI成像方法显示,在小鼠全身注射阿司匹林后,肾髓质和肿瘤周围含有活肿瘤区域血管的高SA积累,与我们之前使用阿司匹林产生的SA作为CEST MRI激活造影剂的研究一致。这种方法提高了定量分析的空间和组织结构准确性,增强了QMALDI成像在研究造影剂、药物分布和各种组织代谢方面的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
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.
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