PET imaging of soluble yttrium-86-labeled carbon nanotubes in mice.

PET imaging of soluble yttrium-86-labeled carbon nanotubes in mice.
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DOI:
10.1371/journal.pone.0000907
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发表时间:
2007-09-19
期刊:
影响因子:
3.7
通讯作者:
Scheinberg DA
Scheinberg DA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
McDevitt MR;Chattopadhyay D;Jaggi JS;Finn RD;Zanzonico PB;Villa C;Rey D;Mendenhall J;Batt CA;Njardarson JT;Scheinberg DA

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纳米材料的潜在医学应用正在塑造纳米生物技术领域的景观并推动其向前发展。决定这些纳米材料适用性的一个关键因素必须是它们如何与生物系统相互作用。单壁碳纳米管(CNT)正在研究作为平台的生物,放射性和化学有效载荷的目标组织的交付。CNT是机械上坚固的石墨烯圆柱体,由sp2键合的碳原子组成,具有高度规则的结构,具有确定的周期性。CNT具有独特的机械化学性质,可用于开发新型药物递送平台。为了评估这种CNT支架的潜在用途,我们进行了成像研究,以确定在小鼠模型中用钇-86和铟-111(分别为86 Y-CNT和111 In-CNT)标记的原型DOTA官能化CNT的组织生物分布和药代动力学。86 Y-CNT构建体由胺官能化的水溶性CNT通过共价连接多个DOTA螯合物拷贝然后用正电子发射金属离子钇-86放射性标记来合成。类似地制备和纯化γ发射111 In-CNT构造。通过光谱学、显微镜和色谱法对构建体进行表征。在注射后3小时和24小时,使用正电子发射断层扫描(PET)表征钇-86的全身分布和清除率。钇-86在3小时内清除血液,并主要分布到肾脏、肝脏、脾脏和骨骼。虽然肾脏中积累的活性随着时间的推移而清除,但全身清除缓慢。静脉或腹膜内注射后,观察到这些靶组织中的差异摄取。全身PET图像表明,86 Y-CNT给药引起的活性积聚的主要部位是肾、肝、脾,以及在很小程度上是骨。血液清除迅速,在诊断应用中使用短寿命放射性核素可能是有益的。
The potential medical applications of nanomaterials are shaping the landscape of the nanobiotechnology field and driving it forward. A key factor in determining the suitability of these nanomaterials must be how they interface with biological systems. Single walled carbon nanotubes (CNT) are being investigated as platforms for the delivery of biological, radiological, and chemical payloads to target tissues. CNT are mechanically robust graphene cylinders comprised of sp2-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. In order to evaluate the potential usefulness of this CNT scaffold, we undertook an imaging study to determine the tissue biodistribution and pharmacokinetics of prototypical DOTA-functionalized CNT labeled with yttrium-86 and indium-111 (86Y-CNT and 111In-CNT, respectively) in a mouse model. The 86Y-CNT construct was synthesized from amine-functionalized, water-soluble CNT by covalently attaching multiple copies of DOTA chelates and then radiolabeling with the positron-emitting metal-ion, yttrium-86. A gamma-emitting 111In-CNT construct was similarly prepared and purified. The constructs were characterized spectroscopically, microscopically, and chromatographically. The whole-body distribution and clearance of yttrium-86 was characterized at 3 and 24 hours post-injection using positron emission tomography (PET). The yttrium-86 cleared the blood within 3 hours and distributed predominantly to the kidneys, liver, spleen and bone. Although the activity that accumulated in the kidney cleared with time, the whole-body clearance was slow. Differential uptake in these target tissues was observed following intraveneous or intraperitoneal injection. The whole-body PET images indicated that the major sites of accumulation of activity resulting from the administration of 86Y-CNT were the kidney, liver, spleen, and to a much less extent the bone. Blood clearance was rapid and could be beneficial in the use of short-lived radionuclides in diagnostic applications.
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期刊: SCIENCE
影响因子: 56.9
作者:
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发表时间: 2006-11-01
影响因子: 1.6
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