AcidoCEST MRI Evaluates the Bone Microenvironment in Multiple Myeloma.
AcidoCEST MRI Evaluates the Bone Microenvironment in Multiple Myeloma.
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DOI：
10.1007/s11307-021-01611-2
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发表时间：
2021-12
影响因子：
3.1
通讯作者：
Chang EY
中科院分区：
文献类型：
--
作者：
Lombardi AF;Wong JH;High R;Ma Y;Jerban S;Tang Q;Du J;Frost P;Pagel MD;Chang EY
多发性骨髓瘤（MM）是骨髓（BM）中恶性浆细胞的不治之症。对缺氧的适应性反应可能是MM进展和耐药性的重要因素。这种代谢适应涉及细胞外pH（pHe）的降低，并且它依赖于在缺氧和癌细胞中常见的葡萄糖转运蛋白（GLUT）的上调。CEST MRI是一种成像技术，通过溶质和水上不稳定质子之间磁饱和转移的交换率间接评估pHe。因此，本研究旨在确定使用MM原位小鼠模型与GLUT 1免疫荧光染色作为参考进行pHe测量的acidoCEST MRI的可行性。使用人RPMI 8226骨髓瘤细胞系在NSG/NOD小鼠中建立原位BM移植的MM异种移植物。在静脉激发后约6周、碘帕醇静脉给药前后进行AcidoCEST MRI。BM pHe值通过用Bloch-McConnell方程拟合CEST光谱来生成。对样本进行脱钙、切片，并对GLUT 1表达进行免疫染色。Pearson相关性用于评估pHe和[H3 O +]与GLUT 1表达之间的关系。10只小鼠接受acidoCEST MRI，然后进行免疫荧光组织学分析。在pHe与GLUT 1表达之间观察到强负相关（r =-0.75，p < 0.001）。在pH转化为[H3 O +]后，观察到[H3 O +]与GLUT 1表达之间的强正相关（r = 0.8，p < 0.001）。AcidoCEST MRI可以测量受多发性骨髓瘤影响的骨髓细胞外pH值。在该MM原位小鼠模型中，通过acidoCEST MRI测量的pHe显示出与通过GLUT 1过表达的免疫荧光组织学评估评估的BM肿瘤代谢表型的强相关性。
Multiple myeloma (MM) is an incurable disease of malignant plasma cells in the bone marrow (BM). Adaptive responses to hypoxia may be an essential element in MM progression and drug resistance. This metabolic adaptation involves a decrease in extracellular pH (pHe), and it depends on the upregulation of glucose transporters (GLUTs) that is common in hypoxia and in cancer cells. CEST MRI is an imaging technique that assesses pHe indirectly by the exchange rate of magnetic saturation transfer between labile protons on a solute and water. Thus, this study aimed to determine the feasibility of acidoCEST MRI for pHe measurement using an orthotopic mouse model of MM compared with GLUT1 immunofluorescence staining as a reference. Orthotopic BM engrafted MM xenografts were established in NSG/NOD mice using the human RPMI8226 myeloma cell line. AcidoCEST MRI was performed approximately six weeks after intravenous challenge, before and after intravenous administration of iopamidol. BM pHe values were generated via fitting the CEST spectrum with the Bloch-McConnell equations. Samples were decalcified, sectioned, and immunostained for GLUT1 expression. Pearson’s correlation was used to assess the relationship between pHe and [H3O+] versus GLUT1 expression. Ten mice underwent acidoCEST MRI followed by immunofluorescent histologic analysis. A strong negative correlation was seen between pHe versus GLUT1 expression (r = − 0.75, p < 0.001). After transformation of pH to [H3O+], a strong positive correlation between [H3O+] and GLUT1 expression was observed (r = 0.8, p < 0.001). AcidoCEST MRI can measure the extracellular pH of bone marrow affected by multiple myeloma. In this MM orthotopic mouse model, pHe measured by acidoCEST MRI showed strong correlations with the metabolic phenotype of BM tumor assessed by immunofluorescent histological assessment of GLUT1 overexpression.
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影响因子：
11.4
作者：
Kumar SK;Lee JH;Lahuerta JJ;Morgan G;Richardson PG;Crowley J;Haessler J;Feather J;Hoering A;Moreau P;LeLeu X;Hulin C;Klein SK;Sonneveld P;Siegel D;Bladé J;Goldschmidt H;Jagannath S;Miguel JS;Orlowski R;Palumbo A;Sezer O;Rajkumar SV;Durie BG;International Myeloma Working Group
通讯作者：
International Myeloma Working Group
影响因子：
--
作者：
Hingorani DV;Montano LA;Randtke EA;Lee YS;Cárdenas-Rodríguez J;Pagel MD
通讯作者：
Pagel MD
影响因子：
5.8
作者：
Lachmann, Alexander;Xu, Huilei;Ma'ayan, Avi
通讯作者：
Ma'ayan, Avi
18F-氟脱氧葡萄糖正电子发射断层扫描可能无法显示放射性肺炎
影响因子：
3.2
作者：
Guo, Meiying;Qi, Liang;Yue, Jinbo
通讯作者：
Yue, Jinbo
影响因子：
2.7
作者：
Matsumoto, Taichi;Jimi, Shiro;Hara, Shuuji
通讯作者：
Hara, Shuuji