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利用与仲氢可逆交换实现超极化的[1-C]丙酮酸-d对乳腺癌代谢异质性进行分子成像。

molecular imaging of breast cancer metabolic heterogeneity using [1-C]pyruvate-d hyperpolarized by reversible exchange with parahydrogen.

作者信息

Petersen Stefan, Nagel Luca, Groß Philipp R, de Maissin Henri, Willing Robert, Heß Lisa, Mitschke Julia, Klemm Nicole, Treiber Judith, Müller Christoph A, Knecht Stephan, Schwartz Ilai, Weigt Moritz, Bock Michael, von Elverfeldt Dominik, Zaitsev Maxim, Chekmenev Eduard Y, Hövener Jan-Bernd, Martins André F, Schilling Franz, Reinheckel Thomas, Schmidt Andreas B

机构信息

Division of Medical Physics, Department of Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Killianstr. 5a, Freiburg 79106, Germany.

Department of Nuclear Medicine, TUM School of Medicine and Health, TUM University Hospital, Technical University of Munich, Munich, Germany, Ismaninger Str. 22, Munich 81675, Germany.

出版信息

Theranostics. 2025 Mar 3;15(9):3714-3723. doi: 10.7150/thno.103272. eCollection 2025.

DOI:10.7150/thno.103272
PMID:40213665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11980672/
Abstract

Metabolic MRI using hyperpolarized (HP) [1-C]pyruvate is promising for diagnostic medicine, allowing the study of cancer metabolism and early detection of therapy response. However, a possible widespread and routine use requires high-throughput and user-friendly technologies to produce the hyperpolarized media. Recently, we introduced a fast (6 min) and cost-effective method using Spin-Lock Induced Crossing and Signal Amplification By Reversible Exchange (SLIC-SABRE) at µT fields and a rapid purification to produce biocompatible HP solutions of aqueous pyruvate. In this study, we used SLIC-SABRE to conduct tumor metabolic imaging in a transgenic breast cancer mouse model (MMTV-PyMT). In agreement with previous HP MRI cancer studies, an elevated lactate metabolism was found in tumors compared to healthy breast tissue, heart, and vasculature, as well as distinct metabolic profiles within different tumor compartments. These findings suggest a potential link between lactate-to-pyruvate ratios and the varying levels of tumor cell proliferation and apoptosis observed by histological analyses. Our results underscore the potential of SABRE to enhance the accessibility and throughput of HP MRI, thereby advancing cancer research and diagnostic oncology.

摘要

使用超极化(HP)[1-C]丙酮酸的代谢磁共振成像在诊断医学方面颇具前景,可用于研究癌症代谢并早期检测治疗反应。然而,要实现广泛且常规的应用,需要高通量且用户友好的技术来制备超极化介质。最近,我们介绍了一种快速(6分钟)且经济高效的方法,即在微特斯拉磁场下利用自旋锁定诱导交叉和可逆交换信号放大(SLIC-SABRE)以及快速纯化,来制备生物相容性的丙酮酸水溶液超极化溶液。在本研究中,我们使用SLIC-SABRE在转基因乳腺癌小鼠模型(MMTV-PyMT)中进行肿瘤代谢成像。与先前的HP MRI癌症研究一致,与健康乳腺组织、心脏和血管相比,肿瘤中乳酸代谢升高,并且在不同肿瘤区域内存在明显的代谢特征。这些发现表明,乳酸与丙酮酸的比率与组织学分析中观察到的肿瘤细胞增殖和凋亡水平的变化之间可能存在联系。我们的结果强调了SABRE在提高HP MRI的可及性和通量方面的潜力,从而推动癌症研究和诊断肿瘤学的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/8940ce9fd0b5/thnov15p3714g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/a6fadd3167fb/thnov15p3714g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/8c503604ba5f/thnov15p3714g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/07a2423c6455/thnov15p3714g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/d10b3a0b83bb/thnov15p3714g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/8940ce9fd0b5/thnov15p3714g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/a6fadd3167fb/thnov15p3714g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/8c503604ba5f/thnov15p3714g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/07a2423c6455/thnov15p3714g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/d10b3a0b83bb/thnov15p3714g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a257/11980672/8940ce9fd0b5/thnov15p3714g005.jpg

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