Lanza Gregory M, Winter Patrick M, Neubauer Anne M, Caruthers Shelton D, Hockett Franklin D, Wickline Samuel A
Division of Cardiology, Washington University Medical School, St. Louis, MO 63110, USA.
Curr Top Dev Biol. 2005;70:57-76. doi: 10.1016/S0070-2153(05)70003-X.
Developments in genomics, proteomics, and cell biology are leading a trend toward individualized segmentation and treatment of patients based on early, noninvasive recognition of unique biosignatures. Although developments in molecular imaging have been dominated by nuclear medicine agents in the past, the advent of nanotechnology in the 1990s has led to magnetic resonance (MR) molecular agents that allow detection of sparse biomarkers with a high-resolution imaging modality that can provide both physiological and functional agents. A wide variety of nanoparticulate MR contrast agents have emerged, most of which are superparamagnetic iron oxide-based constructs. However, this chapter focuses on a diagnostic and therapeutic perfluorocarbon (PFC) nanoparticulate platform that is not only effective as a T1-weighted agent, but also supports (19)F MR spectroscopy and imaging. The unique capability of (19)F permits confirmation and segmentation of MR contrast images as well as direct quantification of nanoparticle concentrations within a voxel. PFC nanoparticles have the capability to effectively deliver therapeutic agents to target sites by a novel mechanism termed "contact-facilitated drug delivery." Combined with MR spectroscopy, the concentration of drug delivered to the target site can be determined and the expected response predicted. Moreover, mixtures of nanoparticles with different perfluorocarbon cores can provide a quantitative, multispectral signal, which can be used to simultaneously distinguish the relative concentrations of several important epitopes within a region of interest. In conjunction with rapid improvements in MR imaging, the prospects for personalized medicine and early recognition and treatment of disease have never been better.
基因组学、蛋白质组学和细胞生物学的发展正引领着一种趋势，即基于对独特生物标志物的早期非侵入性识别，对患者进行个体化的细分和治疗。尽管过去分子成像的发展主要由核医学试剂主导，但20世纪90年代纳米技术的出现催生了磁共振（MR）分子试剂，它能够通过一种高分辨率成像方式检测稀疏的生物标志物，这种成像方式既可以提供生理信息，也可以提供功能信息。各种各样的纳米颗粒MR造影剂应运而生，其中大多数是基于超顺磁性氧化铁的构建体。然而，本章重点介绍一种诊断和治疗用的全氟碳（PFC）纳米颗粒平台，它不仅作为T1加权试剂有效，还支持（19）F磁共振波谱和成像。（19）F的独特能力允许对MR造影图像进行确认和分割，以及直接定量体素内的纳米颗粒浓度。PFC纳米颗粒有能力通过一种称为“接触促进药物递送”的新机制将治疗剂有效递送至靶位点。与磁共振波谱相结合，可以确定递送至靶位点的药物浓度，并预测预期反应。此外，具有不同全氟碳核心的纳米颗粒混合物可以提供定量的多光谱信号，可用于同时区分感兴趣区域内几种重要表位的相对浓度。随着MR成像的迅速改进，个性化医疗以及疾病的早期识别和治疗的前景从未如此美好。
