SMALL ANIMAL PET SCANNER FOR CANCER APPLICATIONS

在过去的十年中，由于细胞和分子生物学的进步，医学经历了深刻而迅速的变化。人类基因组测序的发现以及对新陈代谢和生理学的更好理解促进了“分子医学”的发展。医学的重大进步取决于将新发现从实验室转化为动物模型，然后转化为临床试验。认识到大鼠和小鼠，特别是转基因小鼠，作为分子生物学，遗传学和实验治疗学模型的关键作用，生物工程界一直专注于开发优化用于小动物的小型CT，MRI和PET设备。目前已有几种这样的仪器投入商业使用，有望对生物医学研究产生重大影响。扩大这些设备的使用范围将大大有助于迅速改善对人类疾病的理解和治疗。NIH最近的几项举措强调了开发利用小动物研究模型的成像实验室的重要性。通过允许生物化学和药代动力学的非侵入性体内评价，PET成像可以在评价新药和治疗策略方面具有实质性的实用性。不幸的是，临床PET设备用于实验室动物的临床前研究的适用性受到限制，因为空间分辨率相对于大鼠和小鼠（主要动物模型）的尺寸太粗糙。小型化的小动物PET设备，提供1-2 mm数量级的图像分辨率，将允许对小到老鼠的受试者进行详细的定量研究。南加州大学PET成像科学中心与南加州大学的许多研究人员之间建立了强有力的合作关系，这些研究人员在分子生物学，基因治疗和实验治疗领域处于基础生物科学的前沿。在这些关系中，功能成像发展的主要障碍是目前缺乏非侵入性功能成像，这将允许测量感兴趣的动态代谢和药理学过程，以及在同一实验室动物中连续监测肿瘤生长和治疗反应。本共享仪器提案中要求使用小动物PET成像设备。南加州大学拥有必要的领导，科学研究人员，设备和设施，以提供一个环境，其中小动物PET扫描仪的潜在好处可以充分实现。

Over the last decade, medicine has undergone a profound and rapid change as a result of advances in cellular and molecular biology. Discoveries resulting from the sequencing of the human genome, and a better understanding of metabolism and physiology have contributed to the evolution of "molecular medicine". Significant improvements in medicine have depended upon the translation of new discoveries from the bench-top into animal models and then into clinical trials. Recognizing the key role of rats and mice, especially transgenic mice, as models for molecular biology, genetics and experimental therapeutics, the bioengineering community has focused on the development of miniaturized CT, MRI and PET devices optimized for use with small animals. Several such instruments are now commercially available, which promises to have a major impact on biomedical research. Expanded access to these devices will contribute greatly to the rapid improvement in understanding and treatment of human disease. Several recent NIH initiatives have underscored the importance of developing imaging laboratories that would take advantage of small animal research models. By allowing non-invasive, in vivo evaluation of biochemistry and pharmacokinetics, PET imaging could have substantial utility in evaluating new drugs and treatment strategies. Unfortunately, the applicability of clinical PET devices for preclinical studies with laboratory animals is restricted because the spatial resolution is too coarse relative to the sizes of rats and mice, the predominant animal models. A miniaturized, small animal PET device, offering image resolution on the order of 1-2 mm, would permit detailed, quantitative studies in subjects as small as a mouse. Strong collaborations have been forged between the USC PET Imaging Science Center and the many investigators at USC who are at the forefront of basic biological science in the areas of molecular biology, gene therapy and experimental therapeutics. The primary impediment to the growth of functional imaging within these relationships is the current lack of non-invasive functional imaging, which would permit the measurement of the dynamic metabolic and pharmacologic processes of interest, as well as enable serial monitoring of tumor growth and treatment response within the same laboratory animal. A small animal PET imaging device is requested in this shared instrumentation proposal. USC has the leadership, scientific investigators, equipment and facilities necessary to provide an environment in which the potential benefits of a small animal PET scanner can be fully realized.