Nakajima Takahito, Turkbey Baris, Sano Kohei, Sato Kazuhide, Bernardo Marcelino, Hoyt Robert F, Choyke Peter L, Kobayashi Hisataka
Molecular Imaging Program, NCI, NIH, Bethesda, Maryland, USA.
J Magn Reson Imaging. 2014 Sep;40(3):691-7. doi: 10.1002/jmri.24395. Epub 2013 Oct 10.
To investigate MR lymphangiography in mice and primates with intradermal Gadofosveset and human serum albumin. Gadofosveset is a US FDA approved small molecule Gadolinium (Gd) chelate (957 Da) which reversibly binds serum albumin and temporally behaves as a macromolecule. As the structure of albumin varies among species, the affinity of Gadofosveset is optimized for human albumin. In this study, Gadofosveset premixed with 10% human serum albumin (HSA) was injected intradermally in mice and monkeys, and then MR lymphangiography was performed on a 3.0 Tesla clinical scanner.
Twenty microliters of each agent was injected intradermally at both sides of the front and back paws using a 30-gauge needle into female athymic nude mice (6-8 weeks old, n = 3 mice in each group). The performance of Gadofosveset-HSA was compared with Gd-labeled dendrimers (G4: 6 nm, G6: 10 nm) or Gd-DTPA. The target-to-muscle ratio (TMR = target signal intensity (SI)/muscle SI) was calculated at each time point. The TMRs were compared with a one-way analysis of variance followed by a Bonferroni multiple comparison test.
Images taken as early as 2.5 min after intradermal (id) injection depicted enhanced lymph nodes using Gadofosveset-HSA (2.41 ± 0.20). Up to 7.5 min after injection, TMRs of Gadofosveset-HSA were greater than those of dendrimers (G4 or G6-Gd-DTPA: 2.24 ± 0.10, 2.12 ± 0.11, respectively). By 15 min postinjection, TMRs of Gadofosveset-HSA (2.18 ± 0.19) were comparable to Gd-labeled dendrimers (G4-Gd-DTPA: 2.37 ± 0.15, G6-Gd-DTPA: 2.25 ± 0.18). Gadofosveset-HSA and Gd labeled dendrimers resulted in satisfactory MR lymphography in mice and monkeys.
Because both Gadofosveset and HSA are approved for human use and Gadofosveset clears rapidly through the kidneys, this method has advantages over Gd-dendrimers and could be used for visualizing lymphatic drainage and detecting lymph nodes.
研究用皮内注射钆布醇和人血清白蛋白的方法对小鼠和灵长类动物进行磁共振淋巴造影。钆布醇是一种经美国食品药品监督管理局批准的小分子钆（Gd）螯合物（957道尔顿），它能与血清白蛋白可逆性结合，并在一段时间内表现为大分子。由于白蛋白的结构在不同物种间存在差异，钆布醇对人白蛋白的亲和力已得到优化。在本研究中，将与10%人血清白蛋白（HSA）预混合的钆布醇皮内注射到小鼠和猴子体内，然后在3.0特斯拉临床扫描仪上进行磁共振淋巴造影。
使用30号针头，在雌性无胸腺裸鼠（6 - 8周龄，每组n = 3只小鼠）的前后爪两侧皮内各注射20微升每种试剂。将钆布醇 - HSA的性能与钆标记的树枝状大分子（G4：6纳米，G6：10纳米）或钆 - 二乙三胺五乙酸（Gd - DTPA）进行比较。在每个时间点计算靶 - 肌肉比值（TMR = 靶信号强度（SI）/肌肉SI）。采用单因素方差分析及Bonferroni多重比较检验对TMR进行比较。
皮内（id）注射后最早在2.5分钟拍摄的图像显示，使用钆布醇 - HSA可使淋巴结增强（2.41±0.20）。注射后长达7.5分钟，钆布醇 - HSA的TMR大于树枝状大分子的TMR（G4或G6 - Gd - DTPA分别为2.24±0.10和2.12±0.11）。注射后15分钟时，钆布醇 - HSA的TMR（2.18±0.19）与钆标记的树枝状大分子（G4 - Gd - DTPA：2.37±0.15，G6 - Gd - DTPA：2.25±0.18）相当。钆布醇 - HSA和钆标记的树枝状大分子在小鼠和猴子中均产生了令人满意的磁共振淋巴造影效果。
由于钆布醇和HSA均已获批用于人体，且钆布醇可通过肾脏快速清除，因此该方法优于钆树枝状大分子，可用于可视化淋巴引流和检测淋巴结。
