Sharma Vijay, Luker Gary D, Piwnica-Worms David
Molecular Imaging Center, Mallinckrodt Institute of Radiology and Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri 63110, USA.
J Magn Reson Imaging. 2002 Oct;16(4):336-51. doi: 10.1002/jmri.10182.
Molecular imaging is broadly defined as the characterization and measurement of biological processes in living animals, model systems, and humans at the cellular and molecular level using remote imaging detectors. One underlying premise of molecular imaging is that this emerging field is not defined by the imaging technologies that underpin acquisition of the final image per se, but rather is driven by the underlying biological questions. In practice, the choice of imaging modality and probe is usually reduced to choosing between high spatial resolution and high sensitivity to address a given biological system. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) inherently use image-enhancing agents (radiopharmaceuticals) that are synthesized at sufficiently high specific activity to enable use of tracer concentrations of the compound (picomolar to nanomolar) for detecting molecular signals while providing the desired levels of image contrast. The tracer technologies strategically provide high sensitivity for imaging small-capacity molecular systems in vivo (receptors, enzymes, transporters) at a cost of lower spatial resolution than other technologies. We review several significant PET and SPECT advances in imaging receptors (somatostatin receptor subtypes, neurotensin receptor subtypes, alpha(v)beta(3) integrin), enzymes (hexokinase, thymidine kinase), transporters (MDR1 P-glycoprotein, sodium-iodide symporter), and permeation peptides (human immunodeficiency virus type 1 (HIV-1) Tat conjugates), as well as innovative reporter gene constructs (herpes simplex virus 1 thymidine kinase, somatostatin receptor subtype 2, cytosine deaminase) for imaging gene promoter activation and repression, signal transduction pathways, and protein-protein interactions in vivo.
分子成像被广泛定义为在细胞和分子水平上，使用远程成像探测器对活体动物、模型系统及人类体内的生物过程进行表征和测量。分子成像的一个基本前提是，这个新兴领域并非由构成最终图像采集基础的成像技术本身所定义，而是由其背后的生物学问题所驱动。在实际应用中，成像方式和探针的选择通常归结为在高空间分辨率和高灵敏度之间进行抉择，以解决特定的生物系统问题。正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）本质上使用的是图像增强剂（放射性药物），这些药物以足够高的比活度合成，以便能够使用化合物的示踪剂浓度（皮摩尔到纳摩尔）来检测分子信号，同时提供所需的图像对比度。示踪技术从战略上为体内小容量分子系统（受体、酶、转运体）成像提供了高灵敏度，但代价是空间分辨率低于其他技术。我们综述了PET和SPECT在成像受体（生长抑素受体亚型、神经降压素受体亚型、α(v)β(3)整合素）、酶（己糖激酶、胸苷激酶）、转运体（多药耐药蛋白1 P-糖蛋白、钠碘同向转运体）和渗透肽（人类免疫缺陷病毒1型（HIV-1）Tat缀合物）方面的若干重大进展，以及用于体内成像基因启动子激活和抑制、信号转导途径和蛋白质-蛋白质相互作用的创新报告基因构建体（单纯疱疹病毒1型胸苷激酶、生长抑素受体亚型2、胞嘧啶脱氨酶）。
