Shah Amy T, Demory Beckler Michelle, Walsh Alex J, Jones William P, Pohlmann Paula R, Skala Melissa C
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States of America.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America; Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
PLoS One. 2014 Mar 4;9(3):e90746. doi: 10.1371/journal.pone.0090746. eCollection 2014.
Optical metabolic imaging measures fluorescence intensity and lifetimes from metabolic cofactors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD). These molecular level measurements provide unique biomarkers for early cellular responses to cancer treatments. Head and neck squamous cell carcinoma (HNSCC) is an attractive target for optical imaging because of easy access to the site using fiber optic probes. Two HNSCC cell lines, SCC25 and SCC61, were treated with Cetuximab (anti-EGFR antibody), BGT226 (PI3K/mTOR inhibitor), or cisplatin (chemotherapy) for 24 hours. Results show increased redox ratio, NADH α1 (contribution from free NADH), and FAD α1 (contribution from protein-bound FAD) for malignant cells compared with the nonmalignant cell line OKF6 (p<0.05). In SCC25 and SCC61 cells, the redox ratio is unaffected by cetuximab treatment and decreases with BGT226 and cisplatin treatment (p<0.05), and these results agree with standard measurements of proliferation rates after treatment. For SCC25, NADH α1 is reduced with BGT226 and cisplatin treatment. For SCC61, NADH α1 is reduced with cetuximab, BGT226, and cisplatin treatment. Trends in NADH α1 are statistically similar to changes in standard measurements of glycolytic rates after treatment. FAD α1 is reduced with cisplatin treatment (p<0.05). These shifts in optical endpoints reflect early metabolic changes induced by drug treatment. Overall, these results indicate that optical metabolic imaging has potential to detect early response to cancer treatment in HNSCC, enabling optimal treatment regimens and improved patient outcomes.
光学代谢成像可测量代谢辅助因子烟酰胺腺嘌呤二核苷酸(NADH)和黄素腺嘌呤二核苷酸(FAD)的荧光强度及寿命。这些分子水平的测量为细胞对癌症治疗的早期反应提供了独特的生物标志物。头颈部鳞状细胞癌(HNSCC)是光学成像的一个有吸引力的靶点,因为使用光纤探头很容易到达该部位。两种HNSCC细胞系SCC25和SCC61分别用西妥昔单抗(抗表皮生长因子受体抗体)、BGT226(PI3K/mTOR抑制剂)或顺铂(化疗药物)处理24小时。结果显示,与非恶性细胞系OKF6相比,恶性细胞的氧化还原比、NADHα1(游离NADH的贡献)和FADα1(与蛋白质结合的FAD的贡献)增加(p<0.05)。在SCC25和SCC61细胞中,氧化还原比不受西妥昔单抗处理的影响,而在BGT226和顺铂处理后降低(p<0.05),这些结果与处理后增殖率的标准测量结果一致。对于SCC25,BGT226和顺铂处理后NADHα1降低。对于SCC61,西妥昔单抗、BGT226和顺铂处理后NADHα1降低。NADHα1的变化趋势与处理后糖酵解率的标准测量变化在统计学上相似。顺铂处理后FADα1降低(p<0.05)。这些光学终点的变化反映了药物治疗引起的早期代谢变化。总体而言,这些结果表明光学代谢成像有潜力检测HNSCC对癌症治疗的早期反应,从而实现最佳治疗方案并改善患者预后。