M. Donald Blaufox Laboratory for Molecular Imaging, Department of Nuclear Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Semin Nucl Med. 2011 May;41(3):151-65. doi: 10.1053/j.semnuclmed.2010.12.003.
Imaging devices for small animals have emerged in the past 10 years as extraordinarily useful tools in translational research and drug development. The Food and Drug Administration requires animal testing after in vitro drug discovery but before human application. Many small animal instruments have been developed in analogy to human scale devices, including positron emission tomography, single-photon emission computed tomography, computed tomography, magnetic resonance imaging, and ultrasound. Conversely, optical imaging with fluorescent and bioluminescent tracer technology, originating in single-cell in vitro studies, has been scaled up to whole-body animal imaging. Imaging that uses multiple devices permits a comparison of different aspects of function, anatomy, gene expression, and phenotype by the use of software algorithms or more recently with hybrid instruments. Animal imaging facilitates "bench-to-bedside" drug development in 2 ways. Longitudinal imaging improves the science of animal research through the benefit of paired statistics with the use of animals as their own controls while it simultaneously reduces animal sacrifice. In addition, imaging makes explicit the development of diagnostic and therapeutic agents on nearly identical molecular synthesis platforms, therefore linking drug discovery to the development of imaging tracers. This powerful paradigm, now known as diagnostic/therapeutic pairing or theranostics, is already familiar from the use of (123)I used for thyroid diagnosis and (131)I for therapy of benign and malignant thyroid conditions. Many newer examples exist, such as "cold" or "hot" octreotide and meta-iodobenzylguanidine in neuroendocrine tumors; and rituximab in pharmaceutical doses, or with beta emitter tags, for therapy of indolent non-Hodgkin's lymphoma. Theranostic agents are also rapidly emerging that use nanoparticles, aptamers, peptides, and antibodies for magnetic resonance imaging/positron emission tomography/single-photo emission computed tomography/computed tomography imaging devices in animals with subsequent therapeutic drug development for translation to human use.
在过去的 10 年中，小动物成像设备已经成为转化研究和药物开发中非常有用的工具。食品和药物管理局要求在体外药物发现后但在人类应用前进行动物测试。许多小动物仪器都是根据人体仪器开发的，包括正电子发射断层扫描、单光子发射计算机断层扫描、计算机断层扫描、磁共振成像和超声。相反，源于单细胞体外研究的荧光和生物发光示踪技术的光学成像已经扩展到全身动物成像。使用多种设备进行成像，可以通过使用软件算法或最近使用混合仪器来比较功能、解剖结构、基因表达和表型的不同方面。成像通过使用动物作为自身对照的配对统计数据，同时减少动物牺牲，从而改善动物研究的科学，从而促进“从实验室到病床”的药物开发。此外，成像使诊断和治疗剂的开发几乎在相同的分子合成平台上变得明显，因此将药物发现与成像示踪剂的开发联系起来。这种强大的范例，现在被称为诊断/治疗配对或治疗学，已经从使用 (123)I 用于甲状腺诊断和 (131)I 用于治疗良性和恶性甲状腺疾病中得到熟悉。还有许多更新的例子，如神经内分泌肿瘤中的“冷”或“热”奥曲肽和间碘苄胍；以及利妥昔单抗在药物剂量下，或用β发射体标记，用于治疗惰性非霍奇金淋巴瘤。治疗学试剂也在迅速出现，它们使用纳米粒子、适体、肽和抗体用于动物的磁共振成像/正电子发射断层扫描/单光子发射计算机断层扫描/计算机断层扫描成像设备，随后为转化为人类用途开发治疗药物。
