Small Animal Imaging Shared Resource (SAISR)

小动物成像共享资源（SAISR） 摘要 小动物成像共享资源（SAISR）为以下方面提供仪器、培训和专家支持： UCLA Jonsson Comprehensive Cancer Center（JCCC）研究人员进行的影像学研究。主要 技术和服务包括SAISR发明的微型正电子发射断层扫描（microPET）， 计算机断层扫描（microCT），光学成像（生物发光，荧光和切伦科夫）， 放射自显影成像，以及小分子放射化学和肽/蛋白质的常规生产 放射性标记。SAISR拥有生物医学回旋加速器，生物分子放射性标记设施和设备齐全的 放射化学设施，配有专门设计用于支持PET成像的最先进的放射合成器。三 具体的目标支持SAISR的目标，即为研究人员提供技术成像专业知识， 促进小动物成像研究的设计、执行和分析。目标1：提供和支持 最先进的小动物成像技术;目标2：提供常规放射化学和放射性标记 目标3：为研究人员提供放射化学方面的科学支持和培训， 临床前成像和图像分析。每月两个小时的培训课程向用户介绍最新的成像技术 技术和方法，包括仪器基础，成像生物学，成像程序， 和安全协议 SAISR在项目前期的影响包括SAISR对大卫·内桑森博士的支持 （CMINT）开发新型联合疗法，以靶向多形性胶质母细胞瘤的肿瘤代谢 （GBM）。通过[18 F]FDG（糖酵解的生物标志物）进行GBM葡萄糖利用率快速变化的PET/CT成像， 有效预测体内治疗反应，目前正在临床试验中进行测试（NCT 03732352）。 PET和MRI成像使由Robert Prins博士（CMINT/TI）领导的大型跨项目团队能够 通过PET区分GBM中的炎症反应与MRI所见的其他对比度增强来源。 这两种成像方式的结合区分了肿瘤进展和假进展， 免疫疗法在SAISR和JCCC分子筛选共享资源（MSSR）之间的合作中， 一个由Caius Radu博士领导的跨项目小组（CMINT）开发了一种联合疗法， 使用[18F]FAC PET测定脱氧胞苷激酶（dCK）以评估新型dCK抑制剂的药效学。 后续PET研究表明，dCK有助于癌症的辐射抗性。 从2013年到2018年，SAISR在所有六个项目中支持了42个JCCC成员的项目，占所有项目的84%。 SAISR使用。其中，53%的JCCC用户拥有同行评审的资金。这导致了136份出版物，其中73份 (54%）在高影响力（IF ≥10，或领域领先）期刊。SAISR正准备提交一份NIH共享的 GNEXT PET/CT仪器的仪器补助金，具有目前可用的最高灵敏度， 由SAISR主任Arion Chatzioannou博士发明的技术。

SMALL ANIMAL IMAGING SHARED RESOURCE (SAISR) ABSTRACT The Small Animal Imaging Shared Resource (SAISR) provides instrumentation, training, and expert support for imaging studies conducted by UCLA Jonsson Comprehensive Cancer Center (JCCC) investigators. Major technologies and services include micro-positron emission tomography (microPET), invented at SAISR, micro- computed tomography (microCT), optical imaging (bioluminescence, fluorescence and Cerenkov), autoradiography imaging, and routine production of small molecule radiochemistry and peptide/protein radiolabeling. SAISR has a biomedical cyclotron, biomolecule radiolabeling facility, and a fully equipped radiochemistry facility with state-of-the-art radiosynthesizers specifically designed to support PET imaging. Three specific aims support the SAISR objective of providing investigators with technical imaging expertise and facilitating the design, execution, and analysis of small animal imaging studies. Aim 1: to provide and support state-of-the-art small animal imaging technologies; Aim 2: to provide routine radiochemistry and radiolabeling production services; and Aim 3: to provide investigators with scientific support and training in radiochemistry, preclinical imaging, and image analysis. Monthly two-hour training sessions educate users on the latest imaging technologies and approaches, including topics on instrumentation basics, imaging biology, imaging procedures, and safety protocols. Examples of SAISR impact in the prior project period include SAISR support for David Nathanson, PhD (CMINT) in developing novel combination therapies to target tumor metabolism in glioblastoma multiforme (GBM). PET/CT imaging of rapid changes in GBM glucose utilization by [18F]FDG, a biomarker of glycolysis, effectively predict therapeutic responses in vivo and is currently being tested in a clinical trial (NCT03732352). PET and MRI imaging enabled a large inter-programmatic team led by Robert Prins, PhD (CMINT/TI) to differentiate inflammatory responses in GBM by PET from other sources of contrast-enhancement seen by MRI. The combination of these two imaging modalities distinguished tumor progression from pseudoprogression in immunotherapy. In a collaboration between SAISR and JCCC Molecular Screening Shared Resource (MSSR), an inter-programmatic team led by Caius Radu, MD (CMINT) developed a combination therapy targeting deoxycytidine kinase (dCK) using [18F]FAC PET to assess the pharmacodynamics of novel dCK inhibitors. Follow-on PET studies showed that dCK contributes to radiation resistance in cancer. From 2013 – 2018, SAISR supported projects from 42 JCCC members in all six Programs, representing 84% of SAISR usage. Of this, 53% of JCCC users had peer-reviewed funding. This resulted in 136 publications, with 73 (54%) in high-impact (IF ≥10, or field leading) journals. The SAISR is preparing to submit an NIH shared instrumentation grant for a GNEXT PET/CT instrument, with the highest sensitivity currently available and based on technology invented by SAISR Director Arion Chatziioannou, PhD.