Pre-clinical PET Imaging System

描述(由申请人提供)：随着我们的核医学部最近增加了一个回旋加速器和放射化学设施，圣裘德儿童研究医院的研究人员现在可以使用各种已知和新型的放射性示踪剂用于正电子发射断层扫描(PET)成像。作为本应用程序主题的小动物PET扫描仪被要求扩展我们现有动物成像中心(AIC)的能力，以充分利用新获得的PET放射性示踪剂。我们目前正在参与几个合作项目，使用PET放射性示踪剂进行临床前研究。这些研究虽然非常强大和定量，但也有局限性，因为没有小动物PET扫描仪，它们需要牺牲和解剖被试动物，只在离散的时间点产生数据。PET的真正优势在于能够实时对体内生化过程进行这样的定量测量。此外，能够在同一动物身上进行数小时、数天或数周的重复测量，从而可以评估纵向参数，如治疗反应、特定对象的药物剂量滴定和对刺激反应的生化过程调节。同样，新的治疗发现将受益于使用定制设计的放射性示踪剂对小动物PET进行实时体内药代动力学研究。所有这些后一种研究都更加复杂和昂贵，或者根本不可能使用解剖方法而不是活体成像。此外，我们的机构拥有多种独特的临床前模型(转基因和异种移植)，用于研究疾病过程和测试儿童肿瘤学的新治疗方案。所有这些模型都可以极大地受益于PET成像的独特能力，以加强当前的研究努力。在原位异种移植模型中，评估肿瘤病理生理学的解剖研究(就像我们现在所做的那样)是具有挑战性的，因为在这种模型中，肿瘤的确切位置难以预测。此外，由于动物饲养的成本和难度，非末端成像是转基因模型研究的唯一实用方法。AIC是所有圣裘德调查人员的核心资源，部分资金来自我们NCI综合癌症中心的拨款。我们已经确定了12名教职员工研究人员，他们将是这项核心技术的主要用户，他们中的大多数人已经为一项或多项NIH拨款的研究工作提供了资金，并与圣裘德大学和其他机构的一名或多名研究人员参与了多学科合作项目。他们代表6个学术部门和4个癌症中心项目，在成像、分子和细胞肿瘤学、药代动力学、治疗设计和药物化学方面拥有各种专业知识。增加一台小型动物PET扫描仪将使我们能够充分利用这种合作环境和该机构对核医学研究的投资，并将促进圣裘德对杰出翻译研究的承诺。 公共卫生意义：圣裘德儿童研究医院致力于儿童灾难性疾病的研究和治疗。随着我们核医学部最近增加了一个回旋加速器和放射化学设施，圣裘德儿童研究医院的研究人员现在可以获得各种新的放射性药物，用于医学成像程序，称为正电子发射 体层摄影术。增加一台临床前PET成像相机将使我们能够充分利用最近在核医学研究方面的投资以及我们机构独有的现有各种临床前模型，从而促进圣裘德致力于杰出的转化性研究。

DESCRIPTION (provided by applicant): With the recent addition of a cyclotron and radiochemistry facility to our Nuclear Medicine Division, St Jude Children's Research Hospital investigators now have access to a wide variety of both known and novel radiotracers for positron emission tomography (PET) imaging. The small animal PET scanner that is the subject of this application is requested to expand the capabilities of our existing Animal Imaging Center (AIC) to take full advantage of this newly acquired access to PET radiotracers. We are currently engaged in several collaborative projects using PET radiotracers for preclinical studies. These studies, while very powerful and quantitative, are limited in that without a small animal PET scanner, they require sacrifice and dissection of the subject animals and yield data at only discrete time points. The real strength of PET lies in the ability to make such quantitative measurements of in vivo biochemical processes in real time. Furthermore, the ability to make repeated measurements in the same animal over hours, days or weeks allows assessment of longitudinal parameters such as therapy response, subject-specific titration of drug doses and regulation of biochemical processes in response to stimuli. Similarly, new therapeutic discovery would benefit from the in vivo pharmacokinetic studies possible in real time with small animal PET using custom designed radiotracers. All of these latter studies are much more complex and expensive, or simply impossible, using dissection methods rather than in vivo imaging. In addition, our institution has a diverse collection of unique preclinical models (both transgenic and xenograft) with which to study disease processes and test new therapeutic regimens in pediatric oncology. All of these models could greatly benefit from the unique capabilities of PET imaging to enhance current research efforts. Dissection studies that assess tumor pathophysiology (as we do now) are challenging in orthotopic xenograft models where exact tumor location is less predictable. Furthermore, non-terminal imaging is the only practical method for studies of transgenic models due to the cost and difficulty of animal breeding. The AIC serves as a core resource to all St Jude investigators and is funded in part by our NCI Comprehensive Cancer Center grant. We have identified 12 faculty investigators who would be the primary users of this core technology, most of whom have funded research efforts on one or multiple NIH grants and are engaged in multi-disciplinary collaborative projects with one or more investigators at St Jude and at other institutions. They represent 6 academic departments and 4 Cancer Center Programs with a variety of expertise in imaging, molecular and cellular oncology, pharmacokinetics, therapeutic design and medicinal chemistry. The addition of a small animal PET scanner will allow us to fully capture this environment of collaboration and the institution's investment in Nuclear Medicine research and will facilitate St Jude's commitment to outstanding translational research. PUBLIC HEALTH RELEVANCE: St Jude Children's Research Hospital is dedicated to the study and treatment of catastrophic disease in children. With the recent addition of a cyclotron and radiochemistry facility to our Nuclear Medicine Division, St Jude Children's Research Hospital investigators now have access to a variety of novel radioactive drugs for a medical imaging procedure called positron emission tomography. The addition of a preclinical PET imaging camera will allow us to take full advantage of both this recent investment in Nuclear Medicine research and the existing variety of preclinical models unique to our institution, thus facilitating St Jude's commitment to outstanding translational research.