Magnetic resonance imaging monitors physiological changes with antihedgehog therapy in pancreatic adenocarcinoma xenograft model.
Magnetic resonance imaging monitors physiological changes with antihedgehog therapy in pancreatic adenocarcinoma xenograft model.
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DOI：
10.1097/mpa.0b013e31817c5113
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发表时间：
2008-11
期刊：
影响因子：
2.9
通讯作者：
Thayer SP
中科院分区：
文献类型：
--
作者：
Guimaraes AR;Rakhlin E;Weissleder R;Thayer SP
sonic hedgehog （Shh）通路在胰腺癌（胰腺癌[PDAC]）中具有明确的作用。我们在PDAC异种移植模型中测试了磁性氧化铁纳米颗粒对血管体积分数（VVF）的磁共振成像测量是否对靶向Shh治疗的抗血管生成作用敏感。将胰腺腺癌异种移植细胞系皮下植入裸鼠（4组19个样本）。治疗针对Shh信号通路的3个位点（抗Shh抗体、环巴胺或forskolin）。静脉注射ion -47前后（腹腔注射1周后）行磁共振成像（4.7-T Bruker Pharmascan）。血管体积分数量化为ΔR2（来自多重对比T2序列），并归一化为假定肌肉VVF为3%。线性回归将VVF与微血管密度（MVD）、活腺密度（VGD）和增殖指数（PI）等组织学指标进行比较。在抗hh治疗的反应中，肿瘤显示VGD、PI、MVD和VVF与对照组相比降低（P < 0.001）。将血管体积分数与组织学指标PI （R2 = 0.88， P< 0.05）、VGD （R2 = 0.87， P< 0.05）、MVD （R2 = 0.85， P< 0.05）进行比较。使用磁性氧化铁纳米颗粒进行磁共振成像VVF可以作为对Shh PDAC治疗的生物反应的无创测量，易于转化为临床。
The sonic hedgehog (Shh) pathway has an established role in pancreatic cancer (pancreatic adenocarcinoma [PDAC]). We tested whether magnetic resonance imaging measures of vascular volume fraction (VVF) using magnetic iron oxide nanoparticles are sensitive to the antiangiogenic effect of targeted Shh therapies in a PDAC xenograft model. Pancreatic adenocarcinoma xenograft lines were subcutaneously implanted into nude mice (n = 19 samples within 4 groups). Therapies were targeted to 3 loci of the Shh signaling pathway (anti-Shh antibody, cyclopamine, or forskolin). Magnetic resonance imaging (4.7-T Bruker Pharmascan) was performed (after 1 week of intraperitoneal therapy) before and after intravenous injection of MION-47. Vascular volume fraction was quantified as ΔR2 (from multicontrast T2 sequences) and normalized to an assumed VVF in muscle of 3%. Linear regression compared VVF to histological indices including microvessel density (MVD), viable gland density (VGD), and proliferative index (PI). In response to anti-Hh treatment, tumors showed a decrease in VGD, PI, MVD, and VVF compared with controls (P < 0.001). Vascular volume fraction was compared with histological indicators of response: PI (R2 = 0.88; P < 0.05), VGD (R2 = 0.87; P< 0.05), and MVD (R2 = 0.85; P < 0.05). Magnetic resonance imaging VVF using magnetic iron oxide nanoparticles may serve as a noninvasive measure of biological response to Shh PDAC therapy with easy translation to the clinic.