Pretargeted Positron Emission Tomography Imaging That Employs Supramolecular Nanoparticles with in Vivo Bioorthogonal Chemistry.
Pretargeted Positron Emission Tomography Imaging That Employs Supramolecular Nanoparticles with in Vivo Bioorthogonal Chemistry.
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DOI：
10.1021/acsnano.5b06860
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发表时间：
2016-01-26
期刊：
影响因子：
17.1
通讯作者：
Lin WY
中科院分区：
文献类型：
--
作者：
Hou S;Choi JS;Garcia MA;Xing Y;Chen KJ;Chen YM;Jiang ZK;Ro T;Wu L;Stout DB;Tomlinson JS;Wang H;Chen K;Tseng HR;Lin WY
一个pretargeted肿瘤正电子发射断层扫描（PET）成像，利用超分子纳米粒子的力量与体内生物正交化学证明了临床相关的问题，肿瘤成像。这种方法的优点是：（i）肿瘤靶向剂和显像剂的药代动力学（PK）可以通过化学改变独立改变，以实现所需的体内性能，以及（ii）两种PK和其他可控变量之间的相互作用为改善PET成像提供了第二层控制。简而言之，我们利用超分子化学合成了含有反式环辛烯（TCO，一种生物正交反应基序）的肿瘤靶向纳米颗粒，称为TCO SNPs。在活小鼠的肿瘤中静脉内注射和随后浓缩TCO SNPs后，注射含有互补生物正交基序（四嗪，Tz）和正电子发射放射性同位素（64 Cu）的小分子以选择性地和不可逆地与TCO反应。在快速清除未反应的64 Cu-Tz探针后，完成肿瘤块的高对比度PET成像。由于使用EPR效应，我们的纳米颗粒方法涵盖了更广泛的肿瘤类型，这是大多数实体肿瘤的普遍现象。
A pretargeted oncologic positron emission tomography (PET) imaging that leverages the power of supramolecular nanoparticles with in vivo bioorthogonal chemistry was demonstrated for the clinically relevant problem of tumor imaging. The advantages of this approach are that (i) the pharmacokinetics (PKs) of tumor-targeting and imaging agents can be independently altered via chemical alteration to achieve the desired in vivo performance and (ii) the interplay between the two PKs and other controllable variables confers a second layer of control toward improved PET imaging. In brief, we utilized supramolecular chemistry to synthesize tumor-targeting nanoparticles containing transcyclooctene (TCO, a bioorthogonal reactive motif), called TCO⊂SNPs. After the intravenous injection and subsequent concentration of the TCO⊂SNPs in the tumors of living mice, a small molecule containing both the complementary bioorthogonal motif (tetrazine, Tz) and a positron-emitting radioisotope (64Cu) was injected to react selectively and irreversibly to TCO. High-contrast PET imaging of the tumor mass was accomplished after the rapid clearance of the unreacted 64Cu-Tz probe. Our nanoparticle approach encompasses a wider gamut of tumor types due to the use of EPR effects, which is a universal phenomenon for most solid tumors.