Pretargeted Positron Emission Tomography Imaging That Employs Supramolecular Nanoparticles with in Vivo Bioorthogonal Chemistry

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• 作者：Shuang Hou ; Jin-sil Choi ; Mitch Andre Garcia ; Yan Xing ; Kuan-Ju Chen ; Yi-Ming Chen ; Ziyue K. Jiang ; Tracy Ro ; Lily Wu ; David B. Stout ; James S. Tomlinson ; Hao Wang ; Kai Chen ; Hsian-Rong Tseng ; Wei-Yu Lin
• 刊名：ACS Nano
• 出版年：2016
• 出版时间：January 26, 2016
• 年：2016
• 卷：10
• 期：1
• 页码：1417-1424
• 全文大小：503K
• ISSN：1936-086X

文摘

A pretargeted oncologic positron emission tomography (PET) imaging that leverages the power of supramolecular nanoparticles with <i>in vivoi> 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 <i>viai> chemical alteration to achieve the desired <i>in vivoi> 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.