Tumor Contrast Enhancement and Whole-Body Elimination of the Manganese-Based Magnetic Resonance Imaging Contrast Agent Mn-PyC3A
Tumor Contrast Enhancement and Whole-Body Elimination of the Manganese-Based Magnetic Resonance Imaging Contrast Agent Mn-PyC3A
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DOI：
10.1097/rli.0000000000000593
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发表时间：
2019-11-01
影响因子：
6.7
通讯作者：
Gale, Eric M.
中科院分区：
文献类型：
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作者：
Erstad, Derek J.;Ramsay, Ian A.;Gale, Eric M.
本研究的目的是比较新型锰基磁共振成像（MRI）造影剂Mn-PyC3A与市售钆基造影剂Gd-DOTA和Gd-EOB-DTPA在乳腺癌和转移性肝病小鼠模型中检测肿瘤的效果，并量化Mn-PyC3A在大鼠体内的分数排泄和消除情况。方法将0.1 mmol/kg Mn-PyC3A的t1加权增强MRI与0.1 mmol/kg Gd-DOTA的乳腺癌小鼠模型（n = 8）和0.025 mmol/kg Gd-EOB-DTPA的肝转移小鼠模型（n = 6）进行比较。采用Mn-52计数法或Gd元素分析法，测定大鼠注射2.0 mmol/kg [Mn-52]Mn-PyC3A或Gd- dota后的分步排泄、1 d生物分布和7 d生物分布。影像学资料采用配对t检验进行比较；生物分布资料采用非配对t检验进行比较。结果Mn-PyC3A和Gd-DOTA注射后3分钟肿瘤与肌肉的对比噪声比（Delta CNR）（平均+/-标准差）分别增加17 +/- 3.8和20 +/- 4.4 （P = 0.34）。Mn-PyC3A和Gd-EOB-DTPA注射后8分钟肝脏到肿瘤的δ CNR值分别为28 +/- 9.0和48 +/- 23 （P = 0.11）。给药后，Mn-PyC3A进入尿液的比例为85%，进入粪便的比例为15%。1 d后Mn和Gd在组织中恢复的注射剂量百分比（%ID）分别为0.32 +/- 0.12和0.57 +/- 0.12 (P = 0.0030)， 7 d后分别为0.058 +/- 0.051和0.19 +/- 0.052 （P < 0.0001）。结论Mn-PyC3A在小鼠乳腺癌模型中具有与Gd-DOTA相当的肿瘤增强效果，并且比Gd-DOTA更完全消除肿瘤；部分肝胆清除Mn-PyC3A使肝转移的明显延迟期可视化。
Objectives The goals of this study were to compare the efficacy of the new manganese-based magnetic resonance imaging (MRI) contrast agent Mn-PyC3A to the commercial gadolinium-based agents Gd-DOTA and to Gd-EOB-DTPA to detect tumors in murine models of breast cancer and metastatic liver disease, respectively, and to quantify the fractional excretion and elimination of Mn-PyC3A in rats. Methods T1-weighted contrast-enhanced MRI with 0.1 mmol/kg Mn-PyC3A was compared with 0.1 mmol/kg Gd-DOTA in a breast cancer mouse model (n = 8) and to 0.025 mmol/kg Gd-EOB-DTPA in a liver metastasis mouse model (n = 6). The fractional excretion, 1-day biodistribution, and 7-day biodistribution in rats after injection of 2.0 mmol/kg [Mn-52]Mn-PyC3A or Gd-DOTA were quantified by Mn-52 gamma counting or Gd elemental analysis. Imaging data were compared with a paired t test; biodistribution data were compared with an unpaired t test. Results The postinjection-preinjection increases in tumor-to-muscle contrast-to-noise ratio (Delta CNR) 3 minutes after injection of Mn-PyC3A and Gd-DOTA (mean +/- standard deviation) were 17 +/- 3.8 and 20 +/- 4.4, respectively (P = 0.34). Liver-to-tumor Delta CNR values at 8 minutes postinjection of Mn-PyC3A and Gd-EOB-DTPA were 28 +/- 9.0 and 48 +/- 23, respectively (P = 0.11). Mn-PyC3A is eliminated with 85% into the urine and 15% into the feces after administration to rats. The percentage of the injected doses (%ID) of Mn and Gd recovered in tissues after 1 day were 0.32 +/- 0.12 and 0.57 +/- 0.12, respectively (P = 0.0030), and after 7 days were 0.058 +/- 0.051 and 0.19 +/- 0.052, respectively (P < 0.0001). Conclusions Mn-PyC3A provides comparable tumor contrast enhancement to Gd-DOTA in a mouse breast cancer model and is more completely eliminated than Gd-DOTA; partial hepatobiliary elimination of Mn-PyC3A enables conspicuous delayed phase visualization of liver metastases.