Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI.

Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI.
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DOI:
10.1002/mrm.25053
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发表时间:
2014-11
影响因子:
3.3
通讯作者:
Pagel, Mark D.
Pagel, Mark D.
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Liu Qi;Howison, Christine M.;Jeffery, Justin J.;Robey, Ian F.;Kuo, Phillip H.;Pagel, Mark D.

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需要一种实用的、非侵入性的方法来测量肿瘤体内的细胞外pH值(pHe),以纵向监测肿瘤酸中毒。我们已经优化了一种生物医学成像方法,称为acidoCEST MRI,为乳腺癌临床前模型中的肿瘤pHe提供无创评估。优化了CEST- fisp MRI方法,用于检测临床批准的CT造影剂碘丙胺的两个酰胺质子的化学交换饱和转移(CEST)。使用两种CEST效应的比值来测量ph值。评估碘丙胺的给药途径,以确保药物充分递送到肿瘤。然后采用优化后的acidoCEST MRI方法评估碳酸氢盐碱化治疗后肿瘤pHe的变化。acidoCEST MRI方案测量pH值在6.2和7.2 pH单位之间。大剂量的碘丙胺被证明可以提高肿瘤pHe测量的精度,但该药物对肿瘤pHe没有影响。采用AcidoCEST MRI纵向监测碳酸氢盐治疗对肿瘤和膀胱pHe的影响。本研究表明,优化的acidoCEST MRI方法是评估肿瘤酸中毒变化的实用、无创方法。
A practical, non-invasive method is needed to measure the extracellular pH (pHe) within in vivo tumors to longitudinally monitor tumor acidosis. We have optimized a biomedical imaging method, termed acidoCEST MRI, to provide non-invasive assessments of tumor pHe in pre-clinical models of mammary carcinoma. A CEST-FISP MRI method was optimized to detect the chemical exchange saturation transfer (CEST) of two amide protons of a clinically approved CT contrast agent, iopromide. The ratio of the two CEST effects was used to measure pH. Routes of administration of iopromide were evaluated to ensure sufficient delivery of the agent to the tumor. The optimized acidoCEST MRI method was then used to evaluate the change in tumor pHe following alkalinizing bicarbonate treatment. The acidoCEST MRI protocol measured pH between 6.2 and 7.2 pH units. Greater delivery of iopromide was shown to improve the precision of the measurement of tumor pHe, but the agent did not influence the tumor pHe. AcidoCEST MRI was used to longitudinally monitor the effect of bicarbonate treatment on the pHe of tumors and bladders. This study demonstrates that an optimized acidoCEST MRI method is a practical, non-invasive method for assessing changes in tumor acidosis.
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