Quantitative magnetic resonance and optical imaging biomarkers of melanoma metastatic potential
Quantitative magnetic resonance and optical imaging biomarkers of melanoma metastatic potential
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DOI：
10.1073/pnas.0901807106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Glickson, Jerry D.
中科院分区：
文献类型：
--
作者：
Li, Lin Z.;Zhou, Rong;Glickson, Jerry D.
无创或微创预测肿瘤转移潜力将有助于癌症的个体化管理。对一组人黑色素瘤异种移植物进行了研究，这些移植物跨越了通过体内肺集落测定和体外膜侵袭培养系统测量的全部转移潜力。三种成像方法可能可转移到临床[动态对比增强（DCE）MRI，T-1 rho-MRI和低温荧光成像（可在活检标本上测量）]，区分了裸鼠中相对转移性较低和转移性较高的人黑色素瘤异种移植物。DCE-MRI采用快门速度弛豫算法进行分析，并使用在小鼠心脏左心室中同时测量的动脉输入函数，得到了测量血管灌注/渗透性的血液传输速率常数K-transs。转移性最小的黑色素瘤（A375 P）的核心中的K-transs显著高于转移性最大的黑色素瘤（C8161）的核心。C8161黑色素瘤较A375 P黑色素瘤血管结构多，功能性血管少。A375 P黑色素瘤的平均T-1 rho值显著高于C8161黑色素瘤。T-1和T-2弛豫时间的测量在这2个黑色素瘤之间没有显著差异。线粒体氧化还原比Fp/（Fp + NADH）（其中Fp和NADH分别是氧化黄素蛋白和还原吡啶核苷酸的荧光）与5种黑色素瘤细胞系（A375 P、A375 M、A375 P10、A375 P5和C8161）的体外侵袭潜力呈线性变化。这项研究表明，恶劣的微环境可能会促进黑色素瘤转移，并提供潜在的转移潜力的生物标志物。
Noninvasive or minimally invasive prediction of tumor metastatic potential would facilitate individualized cancer management. Studies were performed on a panel of human melanoma xenografts that spanned the full range of metastatic potential measured by an in vivo lung colony assay and an in vitro membrane invasion culture system. Three imaging methods potentially transferable to the clinic [dynamic contrast-enhanced (DCE) MRI, T-1 rho-MRI, and low-temperature fluorescence imaging (measurable on biopsy specimens)] distinguished between relatively less metastatic and more metastatic human melanoma xenografts in nude mice. DCE-MRI, analyzed with the shutter-speed relaxometric algorithm and using an arterial input function simultaneously measured in the left ventricle of the mouse heart, yielded a blood transfer rate constant, K-trans, that measures vascular perfusion/permeability. K-trans was significantly higher in the core of the least metastatic melanoma (A375P) than in the core of the most metastatic melanoma (C8161). C8161 melanoma had more blood vascular structures but fewer functional blood vessels than A375P melanoma. The A375P melanoma exhibited mean T-1 rho values that were significantly higher than those of C8161 melanoma. Measurements of T-1 and T-2 relaxation times did not differ significantly between these 2 melanomas. The mitochondrial redox ratio, Fp/(Fp + NADH), where Fp and NADH are the fluorescences of oxidized flavoproteins and reduced pyridine nucleotides, respectively, varied linearly with the in vitro invasive potential of the 5 melanoma cell lines (A375P, A375M, A375P10, A375P5, and C8161). This study shows that a harsh microenvironment may promote melanoma metastasis and provides potential biomarkers of metastatic potential.