Iltis Isabelle, Choi Jeunghwan, Vollmers Manda, Shenoi Mithun, Bischof John, Metzger Gregory J
Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA.
NMR Biomed. 2014 Sep;27(9):1063-9. doi: 10.1002/nbm.3157. Epub 2014 Jul 1.
The outcome of systemic and local therapies (e.g. chemotherapy, radiotherapy, surgery, focal ablation) for prostate cancer can be significantly improved by using tumor-specific adjuvants prior to treatment ("preconditioning"). We propose to use dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to monitor the in vivo response of a mouse model of prostate cancer treated with a vascular disruptive agent, TNF-α, delivered on a gold nanoparticle (NP-TNF). Six male nude mice bearing 4-5 week old LNCaP tumors were scanned at 9.4 T. DCE-MRI was performed two days before and 4-5 h after treatment with NP-TNF. An intraperitoneal (i.p.) bolus of gadolinium-DTPA (Gd) was administered and contrast enhancement was measured for 90 min. Concentration-time curves of Gd were calculated and the area under the Gd curve (AUGC) was determined pre- and post-treatment. NP-TNF treatment caused an increase in contrast uptake in tumors. Interestingly, the early concentration (10 min post Gd bolus i.p.) was similar in both untreated and treated conditions; however, 90 min after injection, [Gd] was 3.4 times higher than before treatment. AUGC doubled from (11 ± 6) [Gd] × min before treatment to (22 ± 9) [Gd] × min after treatment. An increase in signal enhancement was also observed in the muscle but to a lesser degree. We also evaluated the kinetics of intravenous Gd administration in mice bearing a jugular vein catheter to mimic the delivery method used in clinical trials. The overall treatment effects were independent of the delivery pathway of the contrast agent. In conclusion, we show that DCE-MRI is suitable to detect changes associated with a vascular disruptive agent in a mouse model of prostate cancer. The ability to characterize the effects of nanoparticle therapy in vivo with non-destructive methods is important, as such compounds, in combination with treatment strategies, are progressing towards clinical trials.
通过在治疗前使用肿瘤特异性佐剂（“预处理”），前列腺癌的全身和局部治疗（如化疗、放疗、手术、局部消融）的效果可以得到显著改善。我们建议使用动态对比增强磁共振成像（DCE-MRI）来监测用载于金纳米颗粒（NP-TNF）上的血管破坏剂TNF-α治疗的前列腺癌小鼠模型的体内反应。六只携带4-5周龄LNCaP肿瘤的雄性裸鼠在9.4T下进行扫描。在NP-TNF治疗前两天和治疗后4-5小时进行DCE-MRI。腹腔内（i.p.）注射钆-DTPA（Gd）推注，并测量90分钟的对比增强。计算Gd的浓度-时间曲线，并在治疗前后确定Gd曲线下面积（AUGC）。NP-TNF治疗导致肿瘤对比剂摄取增加。有趣的是，早期浓度（腹腔内注射Gd推注后10分钟）在未治疗和治疗条件下相似；然而，注射后90分钟，[Gd]比治疗前高3.4倍。AUGC从治疗前的（11±6）[Gd]×分钟增加到治疗后的（22±9）[Gd]×分钟。在肌肉中也观察到信号增强增加，但程度较小。我们还评估了在带有颈静脉导管的小鼠中静脉注射Gd的动力学，以模拟临床试验中使用的给药方法。总体治疗效果与造影剂的给药途径无关。总之，我们表明DCE-MRI适用于检测前列腺癌小鼠模型中与血管破坏剂相关的变化。用非破坏性方法在体内表征纳米颗粒治疗效果的能力很重要，因为此类化合物与治疗策略相结合正在迈向临床试验。
