代谢环境的代谢改变对于肿瘤进展、转移和对靶向治疗的反应具有重要意义，因此，对肿瘤代谢的非侵入性和重复性成像非常重要。本研究的目的是探究多参数化化学交换饱和转移磁共振成像（CEST-MRI）是否能够检测到在不同恶性程度的小鼠乳腺癌模型的肿瘤微环境代谢特征之间的差异，并评估其对免疫治疗的反应。我们研究了高度恶性的4T1和低度恶性的67NR小鼠乳腺癌模型的肿瘤特征，并评估了肿瘤进展和免疫检查点抑制剂治疗期间的变化。为了同时分析不同代谢物，我们进行了多参数化CEST-MRI，计算了葡萄糖加权的1.2至2.0 ppm、肌酸加权的2.0 ppm和酰胺质子转移（APT）加权的3.2至3.6 ppm的不对称磁化率（MTRasym）。通过核磁共振波谱、基质辅助激光解离/电离质谱成像与激光共振离子化后序离子图以及免疫组织化学等方法，我们进行了MRI结果的体外验证。在肿瘤进展过程中，这两个肿瘤模型在所有检测的CEST对比中显示出不同的趋势：4T1模型的葡萄糖和APT对比减少，肌酸对比增加；而67NR肿瘤则在疾病进展过程中葡萄糖和APT对比增加，肌酸对比减少。在治疗开始后的三天内，CEST对比能够捕捉到两个肿瘤模型对免疫检查点抑制剂治疗的反应。多参数化CEST-MRI可以非侵入性地评估TME的代谢特征，既能够评估肿瘤的恶性程度，又能够评估对免疫检查点抑制的早期反应。© 2023. BioMed Central Ltd., part of Springer Nature.

With metabolic alterations of the tumor microenvironment (TME) contributing to cancer progression, metastatic spread and response to targeted therapies, non-invasive and repetitive imaging of tumor metabolism is of major importance. The purpose of this study was to investigate whether multiparametric chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) allows to detect differences in the metabolic profiles of the TME in murine breast cancer models with divergent degrees of malignancy and to assess their response to immunotherapy.Tumor characteristics of highly malignant 4T1 and low malignant 67NR murine breast cancer models were investigated, and their changes during tumor progression and immune checkpoint inhibitor (ICI) treatment were evaluated. For simultaneous analysis of different metabolites, multiparametric CEST-MRI with calculation of asymmetric magnetization transfer ratio (MTRasym) at 1.2 to 2.0 ppm for glucose-weighted, 2.0 ppm for creatine-weighted and 3.2 to 3.6 ppm for amide proton transfer- (APT-) weighted CEST contrast was conducted. Ex vivo validation of MRI results was achieved by 1H nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry imaging with laser postionization and immunohistochemistry.During tumor progression, the two tumor models showed divergent trends for all examined CEST contrasts: While glucose- and APT-weighted CEST contrast decreased and creatine-weighted CEST contrast increased over time in the 4T1 model, 67NR tumors exhibited increased glucose- and APT-weighted CEST contrast during disease progression, accompanied by decreased creatine-weighted CEST contrast. Already three days after treatment initiation, CEST contrasts captured response to ICI therapy in both tumor models.Multiparametric CEST-MRI enables non-invasive assessment of metabolic signatures of the TME, allowing both for estimation of the degree of tumor malignancy and for assessment of early response to immune checkpoint inhibition.© 2023. BioMed Central Ltd., part of Springer Nature.