Name: mr molecular imaging of prostate cancer with a small molecular clt1 peptide targeted contrast agent
Uploaded: 2013-09-03T12:00:00
Description: Watch this Scientific Journal Video about MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent at JoVE.com

这项工作是由美国心脏协会GRA 09春季博士后奖学金（09POST2250268）和NIH R01 CA097465支持的一部分。我们高度赞赏文力博士和维卡斯Gulani博士MRI方案的测试和设置，和Yvonne帕克女士为她的肿瘤植入援助。

改编自前研究11协议。 1。的Gd-DOTA的共轭CLT1肽<ol><li>使用标准的固相肽合成法，从2 - 氯三苯甲基氯树脂（1.0毫摩尔）的Fmoc-保护的氨基酸合成肽CLT1（CGLIIQKNEC）。 </li><li>加入最后的氨基酸后，环化树脂上的线性肽与铊（III）的三氟乙酸盐（1.09克，2.0毫摩尔，2当量）的DMF（20ml）中，在0℃搅拌2小时。 </li><li>接着，共轭的PEG与赖氨酸的顺序来CLT1肽（1.0毫摩尔）在树脂...

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关键步骤 选择适当的生物标志物和靶向小肽 成功开发小尺寸的靶向造影剂，两个关键点需要考虑。首先，要选择合适的分子生物标志物是大量存在于同一点存在于正常组织中病变组织是重要的。我们选择了与癌症相关的生物标志物，凝结血浆蛋白，符合这一要求。其次，所选择的目标明确的小分子药物应具有的生物标志物高结合亲和力，使足?...

癌症相关的分子靶点有效的成像具有重要的意义，以提高癌症的早期检测和诊断的准确性。磁共振成像（MRI）是一种强有力的临床成像模态的高空间分辨率和无电离辐射1。然而，没有针对性的造影剂可用于临床肿瘤MR分子成像。创新设计有针对性的MRI造影剂的发展将大大推进磁共振肿瘤分子成像的应用。已取得显著致力为表达癌细胞表面上的生物标志物的MR成像靶向造影剂。由于MRI和这些生物标志物的低浓度的敏感性相对较低，这是一个挑战，以产生足够的对比度增强，使用小分子靶向造影剂2,3有效MR分子成像。为了得到足够的提高，各种递送系统SUCH为脂质体，纳米粒，并与顺磁性钆（Ⅲ）螯合物高负载聚合物复合物已准备加大在靶位点4,5造影剂的局部浓度。虽然这些递送系统，也能产生在动物模型显著肿瘤的增强，它们的大尺寸导致缓慢和不完全从体内消除，产生有毒的钆（III）离子，这可能会导致严重的安全问题6的长期积累。最近，一些研究表明，MRI的分子成像的限制可以通过选择合适的分子生物标记物具有高的局部表达的病变，并使用小分子试剂，可以容易地排出体外7,8来克服。这些药物的主要特点是，它们针对大​​量存在于同一点存在于正常组织中的患病组织的分子标记。高浓度造影剂可以绑定到这些目标，造成suffi为有效MR分子成像古对比度增强。因为它们的尺寸比肾小球滤过阈值时，未结合的造影剂可以很容易地从主体具有减少背景噪声排出体外。我们已经选择了一个普遍的癌症相关的生物标志物，凝结的血浆蛋白，其中大量存在于肿瘤间质，并且很少出现在正常组织9。我们合成了含小靶向肽CGLIIQKNEC（CLT1），这表现出较强的特异性结合到PC3前列腺肿瘤模型10，和四的Gd-DOTA单酰胺螯合物有针对性的造影剂。在这里，我们为MR肿瘤分子成像技术来检测肿瘤的小鼠的方法。

<table border="1">
		<tbody>
		 <tr>
			<td></td>
			<td></td>
			<td></td>
			<td>REAGENTS</td>
		 </tr>
		 <tr>
			<td>Fmoc protected amino acids</td>
			<td>EMD Chemicals Inc</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>DOTA-tris(t-Bu)</td>
			<td>TCI America</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>PyBOP, HOBt, HBTU</td>
			<td>Nova Biochem</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>DIPEA, Thallium(III) trifluoroacetate, TIS</td>
			<td>Sigma-Aldrich Corp.</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Texas Red, succinimidyl ester, single isomer</td>
			<td>Invitrogen</td>
			<td>T20175</td>
			<td></td>
		 </tr>
		 <tr>
			<td></td>
			<td></td>
			<td></td>
			<td>EQUIPMENTS</td>
		 </tr>
		 <tr>
			<td>Agilent 1100 HPLC system</td>
			<td>Agilent</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>ZORBAX 300SB-C18 PrepHT column</td>
			<td>Agilent</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>ICP-OES Optima 3100XL</td>
			<td>Perkin-Elmer</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>MALDI-TOF mass spectrometer</td>
			<td>Bruker</td>
			<td>AutoflexTM Speed</td>
			<td></td>
		 </tr>
		 <tr>
			<td>Maestro FLEX In Vivo Imaging System</td>
			<td>Cambridge Research &amp; Instrumentation, Inc.</td>
			<td></td>
			<td></td>
		 </tr>
		 <tr>
			<td>Biospec 7T MRI scanner</td>
			<td>Bruker</td>
			<td></td>
			<td></td>
		 </tr>
		</tbody>
 </table>

mr molecular imaging of prostate cancer with a small molecular clt1 peptide targeted contrast agent

肿瘤的细胞外基质具有丰盈癌症相关的蛋白质，可以作为生物标记用于癌症的分子成像的。在这项工作中，我们证明有效MR肿瘤分子影像与靶向的Gd-DOTA单酰胺复合物作为特定于肿瘤间质凝结血浆蛋白有针对性的MRI造影剂的小分子肽。我们进行了评价非侵入性的检测前列腺肿瘤与MRI在小鼠原位PC-3前列腺癌模型中的代理的有效性的实验。靶向造影剂是有效的在0.03毫摩尔GD /公斤的低剂量产生显著肿瘤对比度增强。靶向MRI造影剂的肽前途的前列腺肿瘤MR分子成像。

图1示出合成的靶向造影剂CLT1-DL-（钆-DOTA）4和实验的整体方案的。 CLT1-DL-（的Gd-DOTA） 图4示出高得多的弛豫比临床的Gd-DOTA（表1）。在1.5 T，每钆对T 1弛豫CLT1-DL-PBS中（钆-DOTA）4（pH 7.4）中的比的Gd-DOTA 10的高约3倍。大师成像证实了强特异性德克萨斯结合红标记CLT1（CLT1-TR）对肿瘤有小的结合到正常器官和组织，而对非特定加扰的肽（sCLT1-TR）示...

Watch this Scientific Journal Video about MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent at JoVE.com

MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent

为了证明MR癌分子成像与小肽靶向特定于在小鼠前列腺癌模型的肿瘤间质凝结血浆蛋白的MRI造影剂。

前列腺癌与小分子肽CLT1靶向造影剂的磁共振分子成像

Tumor extracellular  matrix has abundance of cancer related proteins that can be used as biomarkers  for cancer molecular imaging. In this work,  we ...

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